|
1
|
Bello N, Hudu SA, Alshrari AS, Imam MU, Jimoh AO. Overview of Hepatitis B Vaccine Non-Response and Associated B Cell Amnesia: A Scoping Review. Pathogens 2024; 13:554. [PMID: 39057781 PMCID: PMC11279426 DOI: 10.3390/pathogens13070554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 06/18/2024] [Accepted: 06/19/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND The advent of the hepatitis B vaccine has achieved tremendous success in eradicating and reducing the burden of hepatitis B infection, which is the main culprit for hepatocellular carcinoma-one of the most fatal malignancies globally. Response to the vaccine is achieved in about 90-95% of healthy individuals and up to only 50% in immunocompromised patients. This review aimed to provide an overview of hepatitis B vaccine non-response, the mechanisms involved, B cell amnesia, and strategies to overcome it. METHODS Databases, including Google Scholar, PubMed, Scopus, Cochrane, and ClinicalTrials.org, were used to search and retrieve articles using keywords on hepatitis B vaccine non-response and B cell amnesia. The PRISMA guideline was followed in identifying studies, screening, selection, and reporting of findings. RESULTS A total of 133 studies on hepatitis B vaccine non-response, mechanisms, and prevention/management strategies were included in the review after screening and final selection. Factors responsible for hepatitis B vaccine non-response were found to include genetic, immunological factors, and B cell amnesia in healthy individuals. The genetic factors were sex, HLA haplotypes, and genetic polymorphisms in immune response markers (cytokines). Non-response was common in conditions of immunodeficiency, such as renal failure, haemodialysis, celiac disease, inflammatory bowel disease, hepatitis C co-infection, and latent hepatitis B infection. Others included diabetes mellitus and HIV infection. The mechanisms involved were impaired immune response by suppression of response (T helper cells) or induced suppression of response (through regulatory B and T cells). DISCUSSION A comprehensive and careful understanding of the patient factors and the nature of the vaccine contributes to developing effective preventive measures. These include revaccination or booster dose, vaccine administration through the intradermal route, and the use of adjuvants in the vaccine.
Collapse
Affiliation(s)
- Nura Bello
- Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840232, Nigeria;
- Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria 810107, Nigeria
| | - Shuaibu A. Hudu
- Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa 13110, Jordan
- Department of Medical Microbiology and Parasitology, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840232, Nigeria
| | - Ahmed S. Alshrari
- Medical Laboratory Technology Department, Faculty of Applied Medical Science, Northern Border University, Arar 91431, Saudi Arabia;
| | - Mustapha U. Imam
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto 840232, Nigeria;
| | - Abdulgafar O. Jimoh
- Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840232, Nigeria;
| |
Collapse
|
|
2
|
Wu TW, Chou CL, Chen CF, Wang LY. Common Genetic Variants of Response to Hepatitis B Vaccines Correlate with Risks of Chronic Infection of Hepatitis B Virus: A Community-Based Case-Control Study. Int J Mol Sci 2023; 24:ijms24119741. [PMID: 37298692 DOI: 10.3390/ijms24119741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 05/26/2023] [Accepted: 06/02/2023] [Indexed: 06/12/2023] Open
Abstract
Hepatitis B (HB) vaccination effectively reduces the risks of chronic infection with the hepatitis B virus (HBV). It is unknown whether there is a common genetic determinant for response to the HB vaccine and susceptibility to chronic HBV infection. This case-control study, which included 193 chronic HBV carriers and 495 non-carriers, aimed to explore the effects of the most significant single nucleotide polymorphisms (SNPs) in response to the HB vaccine on the risks of chronic HBV infection. Out of 13 tested SNPs, the genotype distributions of four SNPs at the human leukocyte antigen (HLA) class II region, including rs34039593, rs614348, rs7770370, and rs9277535, were significantly different between HBV carriers and non-carriers. The age-sex-adjusted odds ratios (OR) of chronic HBV infection for rs34039593 TG, rs614348 TC, rs7770370 AA, and rs9277535 AA genotypes were 0.51 (95% confidence interval [CI], 0.33-0.79; p = 0.0028), 0.49 (95% CI, 0.32-0.75; p = 6.5 × 10-4), 0.33 (95% CI, 0.18-0.63; p = 7.4 × 10-4), and 0.31 (95% CI, 0.14-0.70; p = 0.0043), respectively. Multivariable analyses showed that rs614348 TC and rs7770370 AA genotypes were significantly independent protectors against chronic HBV infection. The multivariable-adjusted ORs for subjects with none, either one, or both of the protective genotypes were 1.00 (referent), 0.47 (95% CI: 0.32-0.71; p = 3.0 × 10-4), and 0.16 (95% CI: 0.05-0.54; p = 0.0032), respectively. Among eight HBeAg-positive carriers, only one of them carried a protective genotype. This study shows that response to the HB vaccine and susceptibility to chronic HBV infection share common genetic determinants and indicates that HLA class II members are the main responsible host genetic factors.
Collapse
Affiliation(s)
- Tzu-Wei Wu
- Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan
| | - Chao-Liang Chou
- Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan
- Department of Neurology, MacKay Memorial Hospital, New Taipei City 251, Taiwan
| | - Chuen-Fei Chen
- Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan
| | - Li-Yu Wang
- Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan
| |
Collapse
|
|
3
|
Mohammadi H, Alavian SM, Sharafi H. Association of single nucleotide polymorphisms in immune-related genes with spontaneous HBsAg seroconversion: A systematic review and meta-analysis. Int Immunopharmacol 2022; 110:108982. [PMID: 35752129 DOI: 10.1016/j.intimp.2022.108982] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 05/28/2022] [Accepted: 06/15/2022] [Indexed: 11/19/2022]
Abstract
BACKGROUND Studies have reported that the immune system modulation genes are involved in the seroconversion during hepatitis B virus (HBV) infection. Here, a systematic review with meta-analysis is implemented on the association of polymorphisms in immune-related genes with the spontaneous hepatitis B surface antigen (HBsAg) seroconversion. METHODS A systematic literature search was conducted in the main electronic databases of Scopus, PubMed, and Web of Science before May 2022. Pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) were used to evaluate the strength of the association between genetic polymorphisms and the chance of spontaneous HBsAg seroconversion. RESULTS A total of 40 studies finally included for meta-analysis of 2 HLA-DP SNPs, 2 HLA-DQ SNPs, 3 IFNL3/4 SNPs, 2 IL10 SNPs, and 5 TNF SNPs. Based on the overall pooled analysis, HLA-DP rs3077 A (OR = 1.47, 95%CI: 1.32-1.65), HLA-DP rs9277535 A (OR = 1.48, 95%CI: 1.32-1.66), HLA-DQ rs2856718 G (OR = 1.37, 95%CI: 1.18-1.59), HLA-DQ rs7453920 A (OR = 1.41, 95%CI: 1.04-1.93), IFNL3/4 rs12980275 G (OR = 1.26, 95%CI: 1.01-1.58), TNFA rs1799964 T (OR = 1.17, 95%CI: 1.02-1.35), and TNFA rs1800630 C (OR = 1.26, 95%CI: 1.03-1.55) increased significantly the chance of spontaneous HBsAg seroconversion. CONCLUSION This meta-analysis showed that the HLA-DP gene rs3077 and rs9277535 SNPs, HLA-DQ gene rs2856718 and rs7453920 SNPs, IFNL3/4 gene rs12980275 SNP, TNFA gene rs1799964 and rs1800630 SNPs are involved in the spontaneous HBsAg seroconversion.
Collapse
Affiliation(s)
- Hamed Mohammadi
- Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran; Department of Immunology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
| | - Seyed Moayed Alavian
- Middle East Liver Diseases (MELD) Center, Tehran, Iran; Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Baqiyatallah University of Medical Sciences, Tehran, Iran
| | | |
Collapse
|
|
4
|
Identified a disintegrin and metalloproteinase with thrombospondin motifs 6 serve as a novel gastric cancer prognostic biomarker by bioinformatics analysis. Biosci Rep 2021; 41:228334. [PMID: 33851708 PMCID: PMC8065180 DOI: 10.1042/bsr20204359] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Revised: 04/01/2021] [Accepted: 04/06/2021] [Indexed: 12/15/2022] Open
Abstract
Objective: We aimed to explore the prognostic value of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) genes in gastric cancer (GC). Methods: The RNA-sequencing (RNA-seq) expression data for 351 GC patients and other relevant clinical data were acquired from The Cancer Genome Atlas (TCGA). Survival analysis and a genome-wide gene set enrichment analysis (GSEA) were performed to define the underlying molecular value of the ADAMTS genes in GC development. Besides, qRT-PCR and immunohistochemistry were all employed to validate the relationship between the expression of these genes and GC patient prognosis. Results: The Log rank test with both Cox regression and Kaplan–Meier survival analyses showed that ADAMTS6 expression profile correlated with the GC patients clinical outcome. Patients with a high expression of ADAMTS6 were associated with poor overall survival (OS). Comprehensive survival analysis of the ADAMTS genes suggests that ADAMTS6 might be an independent predictive factor for the OS in patients with GC. Besides, GSEA demonstrated that ADAMTS6 might be involved in multiple biological processes and pathways, such as the vascular endothelial growth factor A (VEGFA), kirsten rat sarcoma viral oncogene (KRAS), tumor protein P53, c-Jun N-terminal kinase (JNK), cadherin (CDH1) or tumor necrosis factor (TNF) pathways. It was also confirmed by immunohistochemistry and qRT-PCR that ADAMTS6 is highly expressed in GC, which may be related to the prognosis of GC patients. Conclusion: In summary, our study demonstrated that ADAMTS6 gene could be used as a potential molecular marker for GC prognosis.
Collapse
|
|
5
|
Variation and expression of HLA-DPB1 gene in HBV infection. Immunogenetics 2021; 73:253-261. [PMID: 33710355 DOI: 10.1007/s00251-021-01213-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Accepted: 03/01/2021] [Indexed: 12/24/2022]
Abstract
Hepatitis B virus (HBV) affects approximately 68 million people in China, and 10-15% of adults infected with HBV develop chronic hepatitis B, liver cirrhosis, liver failure or hepatocellular carcinoma (HCC). HLA-DPB1 gene polymorphism and expression have been shown to be associated with HBV infection susceptibility and spontaneous clearance. The aim of this study is to evaluate the role of HLA-DPB1 gene polymorphism in HBV infection. HLA-DPB1 and rs9277535 polymorphisms were investigated in 259 patients with HBV infection and 442 healthy controls (HCs) using sequence-based typing. The mRNA of HLA-DPB1 was measured by real-time polymerase chain reaction. HLA-DPB1 genes and rs9277535 polymorphisms were all associated with HBV infection in the Sichuan Han population. rs9277535A and HLA-DPB1*04:02 played a protective role against HBV infection. rs9277535G and DPB1*05:01 were associated with susceptibility to HBV infection. rs9277535GG had significantly higher HLA-DPB1 mRNA expression in the HBV infection group compared with the HC group. HLA-DPB1*05:01 and HLA-DPB1*21:01 had significantly lower mRNA expression in the HBV infection group compared with the HC group. The meta-analysis revealed that HLA-DPB1*02:01, HLA-DPB1*02:02, HAL-DPB1*04:01 and HLA-DPB1*04:02 protected against HBV infection, while HLA-DPB1*05:01, HLA-DPB1*09:01, and HLA-DPB1*13:01 were risk factors for susceptibility to HBV infection. HLA-DPB1*02:01, HLA-DPB1*02:02, and HLA-DPB1*04:01 were associated with HBV spontaneous clearance, while HLA-DPB1*05:01 was associated with chronic HBV infection. HLA-DPB1 alleles and rs9277535 have a major effect on the risk of HBV infection, and HBV infection is associated with lower HLA-DPB1 expression. HLA-DPB1 alleles have an important role in HBV susceptibility and spontaneous clearance.
Collapse
|
|
6
|
Yang H, Yang Y, Dou J, Cui R, Cheng Z, Han Z, Liu F, Yu X, Zhou X, Yu J, Liang P. Cholecystectomy is associated with higher risk of recurrence after microwave ablation of hepatocellular carcinoma: a propensity score matching analysis. Cancer Biol Med 2020; 17:478-491. [PMID: 32587783 PMCID: PMC7309471 DOI: 10.20892/j.issn.2095-3941.2019.0246] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Accepted: 10/07/2019] [Indexed: 12/16/2022] Open
Abstract
Objective: To explore the association between cholecystectomy and the prognostic outcomes of patients with hepatocellular carcinoma (HCC) who underwent microwave ablation (MWA). Methods: Patients with HCC (n = 921) who underwent MWA were included and divided into cholecystectomy (n = 114) and non-cholecystectomy groups (n = 807). After propensity score matching (PSM) at a 1:2 ratio, overall survival (OS) and disease-free survival (DFS) rates were analyzed to compare prognostic outcomes between the cholecystectomy (n = 114) and non-cholecystectomy groups (n = 228). Univariate and multivariate Cox analyses were performed to assess potential risk factors for OS and DFS. Major complications were also compared between the groups. Results: After matching, no significant differences between groups were observed in baseline characteristics. The 1-, 3-, and 5-year OS rates were 96.5%, 82.1%, and 67.1% in the cholecystectomy group, and 97.4%, 85.2%, and 74.4% in the non-cholecystectomy group (P = 0.396); the 1-, 3-, and 5-year DFS rates were 58.4%, 34.5%, and 26.6% in the cholecystectomy group, and 73.6%, 44.7%, and 32.2% in the non-cholecystectomy group (P = 0.026), respectively. The intrahepatic distant recurrence rate in the cholecystectomy group was significantly higher than that in the non-cholecystectomy group (P = 0.026), and the local tumor recurrence and extrahepatic recurrence rates did not significantly differ between the groups (P = 0.609 and P = 0.879). Multivariate analysis revealed that cholecystectomy (HR = 1.364, 95% CI 1.023–1.819, P = 0.035), number of tumors (2 vs. 1: HR = 2.744, 95% CI 1.925–3.912, P < 0.001; 3 vs. 1: HR = 3.411, 95% CI 2.021–5.759, P < 0.001), and γ-GT levels (HR = 1.003, 95% CI 1.000–1.006, P < 0.024) were independent risk factors for DFS. The best γ-GT level cut-off value for predicting median DFS was 39.6 U/L (area under the curve = 0.600, P < 0.05). A positive correlation was observed between cholecystectomy and γ-GT level (r = 0.108, 95% CI −0.001–0.214, P = 0.047). Subgroup analysis showed that the DFS rates were significantly higher in the non-cholecystectomy group than the cholecystectomy group when γ-GT ≥39.6 U/L (P = 0.044). The 5-, 10-, 15-, 20-, and 25-year recurrence rates from the time of cholecystectomy were 2.63%, 21.93%, 42.11%, 58.77%, and 65.79%, respectively. A significant positive correlation was observed between cholecystectomy and the time from cholecystectomy to recurrence (r = 0.205, 95% CI 0.016–0.379, P = 0.029). There were no significant differences in complications between groups (P = 0.685). Conclusions: Patients with HCC who underwent cholecystectomy were more likely to develop intrahepatic distant recurrence after MWA, an outcome probably associated with increased γ-GT levels. Moreover, the recurrence rates increased with time.
Collapse
Affiliation(s)
- Hongcai Yang
- School of Medicine, Nankai University, Tianjin 300071, China.,Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing 100853, China
| | - Yi Yang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jianping Dou
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing 100853, China
| | - Rui Cui
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing 100853, China
| | - Zhigang Cheng
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing 100853, China
| | - Zhiyu Han
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing 100853, China
| | - Fangyi Liu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing 100853, China
| | - Xiaoling Yu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing 100853, China
| | - Xiang Zhou
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jie Yu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing 100853, China
| | - Ping Liang
- School of Medicine, Nankai University, Tianjin 300071, China.,Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing 100853, China
| |
Collapse
|
|
7
|
An P, Zeng Z, Winkler CA. The Loss-of-Function S267F Variant in HBV Receptor NTCP Reduces Human Risk for HBV Infection and Disease Progression. J Infect Dis 2019; 218:1404-1410. [PMID: 29905807 DOI: 10.1093/infdis/jiy355] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Accepted: 06/11/2018] [Indexed: 02/07/2023] Open
Abstract
Background Sodium taurocholate cotransporting polypeptide (NTCP, SLC10A1) is a hepatocyte receptor for hepatitis B virus (HBV) infection. The natural NTCP S267F variant causes loss of NTCP HBV receptor function. We assessed the association of S267F with HBV resistance, HBV infection clearance, and HBV-related cirrhosis and hepatocellular carcinoma (HCC). Methods We tested the effects of S267F in 1117 Han Chinese patients with various HBV infection outcomes using multivariate logistic regression analysis. Results The frequency of S267F (T allele) was higher in HBV-resistant healthy controls (n = 179, 4.0%) compared to HBV-infected patients (n = 648, 1.5%); odds ratio (OR) 0.32 (95% confidence interval [CI] 0.15-0.68; P = .003; dominant model). 267F variant genotypes were also associated with reduced risk for cirrhosis (n = 192, 0.5%) and HCC (n = 258, 1.0%) compared to those with chronic HBV infection (n = 202, 3.0%); OR 0.15 (95% CI, 0.03-0.70) and OR 0.21 (95% CI, 0.062-0.72), respectively. There was no association of the S267F variant with spontaneous HBV clearance. Conclusion The S267F variant for the HBV cell-entry receptor NTCP was associated with increased resistance to HBV infection and decreased risk for cirrhosis and liver cancer among those with chronic HBV infection.
Collapse
Affiliation(s)
- Ping An
- Basic Research Laboratory, Center for Cancer Research, National Cancer Institute.,Basic Science Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland
| | - Zheng Zeng
- Department of Infectious Diseases, Peking University First Hospital, Beijing, China
| | - Cheryl A Winkler
- Basic Research Laboratory, Center for Cancer Research, National Cancer Institute.,Basic Science Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland
| |
Collapse
|
|
8
|
Zhang Z, Wang C, Liu Z, Zou G, Li J, Lu M. Host Genetic Determinants of Hepatitis B Virus Infection. Front Genet 2019; 10:696. [PMID: 31475028 PMCID: PMC6702792 DOI: 10.3389/fgene.2019.00696] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 07/03/2019] [Indexed: 12/14/2022] Open
Abstract
Chronic hepatitis B virus (HBV) infection is still a major health problem worldwide. Recently, a great number of genetic studies based on single nucleotide polymorphisms (SNPs) and genome-wide association studies have been performed to search for host determinants of the development of chronic HBV infection, clinical outcomes, therapeutic efficacy, and responses to hepatitis B vaccines, with a focus on human leukocyte antigens (HLA), cytokine genes, and toll-like receptors. In addition to SNPs, gene insertions/deletions and copy number variants are associated with infection. However, conflicting results have been obtained. In the present review, we summarize the current state of research on host genetic factors and chronic HBV infection, its clinical type, therapies, and hepatitis B vaccine responses and classify published results according to their reliability. The potential roles of host genetic determinants of chronic HBV infection identified in these studies and their clinical significance are discussed. In particular, HLAs were relevant for HBV infection and pathogenesis. Finally, we highlight the need for additional studies with large sample sizes, well-matched study designs, appropriate statistical methods, and validation in multiple populations to improve the treatment of HBV infection.
Collapse
Affiliation(s)
- Zhenhua Zhang
- Department of Infectious Diseases, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
- College of Pharmacy, Anhui Medical University, Hefei, China
| | - Changtai Wang
- Department of Infectious Diseases, the Affiliated Anqing Hospital of Anhui Medical University, Anqing, China
| | - Zhongping Liu
- Department of Infectious Diseases, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Guizhou Zou
- Department of Infectious Diseases, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Jun Li
- College of Pharmacy, Anhui Medical University, Hefei, China
| | - Mengji Lu
- Institute of Virology, University Hospital of Duisburg-Essen, Essen, Germany
| |
Collapse
|
|
9
|
Zhou L, Ren JH, Cheng ST, Xu HM, Chen WX, Chen DP, Wong VKW, Law BYK, Liu Y, Cai XF, Tang H, Yu HB, Hu JL, Hu Y, Zhou HZ, Ren F, He L, Hu ZW, Jiang H, Xu HY, Huang AL, Chen J. A Functional Variant in Ubiquitin Conjugating Enzyme E2 L3 Contributes to Hepatitis B Virus Infection and Maintains Covalently Closed Circular DNA Stability by Inducing Degradation of Apolipoprotein B mRNA Editing Enzyme Catalytic Subunit 3A. Hepatology 2019; 69:1885-1902. [PMID: 30614547 DOI: 10.1002/hep.30497] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Accepted: 12/20/2018] [Indexed: 12/11/2022]
Abstract
Hepatitis B virus (HBV) infection is a common infectious disease, in which nuclear covalently closed circular DNA (cccDNA) plays a key role in viral persistence, viral reactivation after treatment withdrawal, and drug resistance. A recent genome-wide association study has identified that the ubiquitin conjugating enzyme E2 L3 (UBE2L3) gene is associated with increased susceptibility to chronic HBV (CHB) infection in adults. However, the association between UBE2L3 and children with CHB and the underlying mechanism remain unclear. In this study, we performed two-stage case-control studies including adults and independent children in the Chinese Han population. The rs59391722 allele in the promoter of the UBE2L3 gene was significantly associated with HBV infection in both adults and children, and it increased the promoter activity of UBE2L3. Serum UBE2L3 protein levels were positively correlated with HBV viral load and hepatitis B e antigen (HBeAg) levels in children with CHB. In an HBV infection cell model, UBE2L3 knockdown significantly reduced total HBV RNAs, 3.5-kb RNA, as well as cccDNA in HBV-infected HepG2-Na+ /taurocholate cotransporting polypeptide cells and human primary hepatocytes. A mechanistic study found that UBE2L3 maintained cccDNA stability by inducing proteasome-dependent degradation of apolipoprotein B mRNA editing enzyme catalytic subunit 3A, which is responsible for the degradation of HBV cccDNA. Moreover, interferon-α (IFN-α) treatment markedly decreased UBE2L3 expression, while UBE2L3 silencing reinforced the antiviral activity of IFN-α on HBV RNAs, cccDNA, and DNA. rs59391722 in UBE2L3 was correlated with HBV DNA suppression and HBeAg loss in response to IFN-α treatment of children with CHB. Conclusion: These findings highlight a host gene, UBE2L3, contributing to the susceptibility to persistent HBV infection; UBE2L3 may be involved in IFN-mediated viral suppression and serve as a potential target in the prevention and treatment of HBV infection.
Collapse
Affiliation(s)
- Li Zhou
- The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
- Department of Epidemiology, School of Public Health and Management, Chongqing Medical University, Chongqing, China
| | - Ji-Hua Ren
- The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Sheng-Tao Cheng
- The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Hong-Mei Xu
- Department of Infectious Diseases, The Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Wei-Xian Chen
- Department of Clinical Laboratory, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Da-Peng Chen
- Department of Clinical Laboratory, The Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Vincent Kam Wai Wong
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
| | - Betty Yuen Kwan Law
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
| | - Yi Liu
- The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Xue-Fei Cai
- The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Hua Tang
- The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Hai-Bo Yu
- The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Jie-Li Hu
- The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Yuan Hu
- The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Hong-Zhong Zhou
- The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Fang Ren
- The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Lin He
- The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Zhong-Wen Hu
- The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Hui Jiang
- The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Hong-Yan Xu
- The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Ai-Long Huang
- The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Juan Chen
- The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| |
Collapse
|
|
10
|
Gameel TA, Rady S, ElBahnasy KA, Kamal SM. Novel Biomarkers from genes in the apoptotic pathway for Prediction of HCC Progression using Association Rule Mining. PROCEEDINGS OF THE 2019 8TH INTERNATIONAL CONFERENCE ON SOFTWARE AND INFORMATION ENGINEERING 2019:217-221. [DOI: 10.1145/3328833.3328863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Affiliation(s)
| | - Sherine Rady
- Information Systems Department, Ain Shams University, Cairo, Egypt and The British University in Egypt, ICS-BUE, Egypt
| | | | - Sanaa M. Kamal
- Department of Gastroenterology and Tropical Medicine, Ain Shams University, Cairo, Egypt
| |
Collapse
|
|
11
|
Qu S, Wu J, Bao Q, Yao B, Duan R, Chen X, Li L, Yuan H, Jin Y, Ma C. Osterix promotes the migration and angiogenesis of breast cancer by upregulation of S100A4 expression. J Cell Mol Med 2019; 23:1116-1127. [PMID: 30450809 PMCID: PMC6349213 DOI: 10.1111/jcmm.14012] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2018] [Revised: 07/19/2018] [Accepted: 09/12/2018] [Indexed: 11/26/2022] Open
Abstract
As a key transcription factor required for bone formation, osterix (OSX) has been reported to be overexpressed in various cancers, however, its roles in breast cancer progression remain poorly understood. In this study, we demonstrated that OSX was highly expressed in metastatic breast cancer cells. Moreover, it could upregulate the expression of S100 calcium binding protein A4 (S100A4) and potentiate breast cancer cell migration and tumor angiogenesis in vitro and in vivo. Importantly, inhibition of S100A4 impaired OSX-induced cell migration and capillary-like tube formation. Restored S100A4 expression rescued OSX-short hairpin RNA-suppressed cell migration and capillary-like tube formation. Moreover, the expression levels of OSX and S100A4 correlated significantly in human breast tumors. Our study suggested that OSX acts as an oncogenic driver in cell migration and tumor angiogenesis, and may serve as a potential therapeutic target for human breast cancer treatment.
Collapse
Affiliation(s)
- Shuang Qu
- Jiangsu Key Laboratory of XenotransplantationNanjing Medical UniversityNanjingChina
- Department of Medical GeneticsNanjing Medical UniversityNanjingChina
| | - Jiahui Wu
- Jiangsu Key Laboratory of XenotransplantationNanjing Medical UniversityNanjingChina
- Department of Medical GeneticsNanjing Medical UniversityNanjingChina
| | - Qianyi Bao
- Jiangsu Key Laboratory of XenotransplantationNanjing Medical UniversityNanjingChina
- Department of Medical GeneticsNanjing Medical UniversityNanjingChina
| | - Bing Yao
- Jiangsu Key Laboratory of XenotransplantationNanjing Medical UniversityNanjingChina
- Department of Medical GeneticsNanjing Medical UniversityNanjingChina
| | - Rui Duan
- Jiangsu Key Laboratory of XenotransplantationNanjing Medical UniversityNanjingChina
- Department of Medical GeneticsNanjing Medical UniversityNanjingChina
| | - Xiang Chen
- Department of General SurgeryThe Affiliated Yixing Hospital of Jiangsu UniversityYixingChina
| | - Lingyun Li
- Jiangsu Key Laboratory of XenotransplantationNanjing Medical UniversityNanjingChina
- Department of Medical GeneticsNanjing Medical UniversityNanjingChina
| | - Hongyan Yuan
- Department of Oncology and Lombardi Comprehensive Cancer CenterLombardi Comprehensive Cancer CenterWashingtonDistrict of Columbia
| | - Yucui Jin
- Jiangsu Key Laboratory of XenotransplantationNanjing Medical UniversityNanjingChina
- Department of Medical GeneticsNanjing Medical UniversityNanjingChina
| | - Changyan Ma
- Jiangsu Key Laboratory of XenotransplantationNanjing Medical UniversityNanjingChina
- Department of Medical GeneticsNanjing Medical UniversityNanjingChina
| |
Collapse
|
|
12
|
Ou G, Liu X, Yang L, Yu H, Ji X, Liu F, Xu H, Qian L, Wang J, Liu Z. Relationship between HLA-DPA1 mRNA expression and susceptibility to hepatitis B. J Viral Hepat 2019; 26:155-161. [PMID: 30267609 DOI: 10.1111/jvh.13012] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Accepted: 09/07/2018] [Indexed: 12/12/2022]
Abstract
Chronic hepatitis B virus (HBV) infection is influenced by both viral and host factors. In genome-wide association studies, the human leucocyte antigen HLA-DPA1 and related polymorphism rs3077 were found to be associated with susceptibility to and spontaneous clearance of HBV infection. Here, we evaluated the association between HLA-DPA1 mRNA expression and the risk of HBV infection. HLA-DPA1 and rs3077 polymorphisms were investigated in 169 patients with chronic HBV and 217 healthy controls (HCs) from Sichuan Han blood donors using sequence-based typing and meta-analysis for HLA-DPA1 alleles. HLA-DPA1 mRNA levels were measured by real-time polymerase chain reaction. The results showed that HLA-DPA1 and rs3077 were associated with HBV infection in the Sichuan population. Rs3077T and DPA1*01:03 played protective roles in HBV infection, and rs3077C and DPA1*02:02 increased susceptibility to HBV infection. We found that the HLA-DPA1 mRNA expression was decreased in the CHB group; in particular, the 3077CT, 3077TT, DPA1*01:03 and DPA1*02:01 alleles showed a significant decrease. Our results demonstrated, for the first time, that expression of HLA-DPA1 alleles and rs3077 affected the risk of HBV infection. Genotypes with lower HLA-DPA1 expression had a greater susceptibility to HBV infection. Thus, further independent studies are needed to strengthen the associations of these polymorphisms with susceptibility to and clearance of HBV infection in Chinese populations.
Collapse
Affiliation(s)
- Guojin Ou
- Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, China.,Clinical Blood Transfusion Research Center, Institute of Blood Transfusion, CAMS & PUMC, Chengdu, China.,Key Laboratory of Transfusion Adverse Reactions, CAMS, Chengdu, China.,Key Laboratory of Birth Defects and Related Diseases of Women and Children, (Sichuan University), Ministry of Education, Chengdu, China
| | - Xiao Liu
- Deyang People's Hospital, Deyang, China
| | - Liu Yang
- Tianfu New District People's Hospital, Chengdu, China
| | - Hao Yu
- Clinical Blood Transfusion Research Center, Institute of Blood Transfusion, CAMS & PUMC, Chengdu, China.,Key Laboratory of Transfusion Adverse Reactions, CAMS, Chengdu, China
| | - Xin Ji
- Clinical Blood Transfusion Research Center, Institute of Blood Transfusion, CAMS & PUMC, Chengdu, China.,Key Laboratory of Transfusion Adverse Reactions, CAMS, Chengdu, China
| | - Fan Liu
- Clinical Blood Transfusion Research Center, Institute of Blood Transfusion, CAMS & PUMC, Chengdu, China.,Key Laboratory of Transfusion Adverse Reactions, CAMS, Chengdu, China
| | - Haixia Xu
- Clinical Blood Transfusion Research Center, Institute of Blood Transfusion, CAMS & PUMC, Chengdu, China.,Key Laboratory of Transfusion Adverse Reactions, CAMS, Chengdu, China
| | | | - Jue Wang
- Clinical Blood Transfusion Research Center, Institute of Blood Transfusion, CAMS & PUMC, Chengdu, China.,Key Laboratory of Transfusion Adverse Reactions, CAMS, Chengdu, China
| | - Zhong Liu
- Clinical Blood Transfusion Research Center, Institute of Blood Transfusion, CAMS & PUMC, Chengdu, China.,Key Laboratory of Transfusion Adverse Reactions, CAMS, Chengdu, China
| |
Collapse
|
|
13
|
Akcay IM, Katrinli S, Ozdil K, Doganay GD, Doganay L. Host genetic factors affecting hepatitis B infection outcomes: Insights from genome-wide association studies. World J Gastroenterol 2018; 24:3347-3360. [PMID: 30122875 PMCID: PMC6092584 DOI: 10.3748/wjg.v24.i30.3347] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Revised: 05/29/2018] [Accepted: 06/25/2018] [Indexed: 02/06/2023] Open
Abstract
The clinical outcome of Hepatitis B Virus (HBV) infection depends on the success or failure of the immune responses to HBV, and varies widely among individuals, ranging from asymptomatic self-limited infection, inactive carrier state, chronic hepatitis, cirrhosis, hepatocellular carcinoma, to liver failure. Genome-wide association studies (GWAS) identified key genetic factors influencing the pathogenesis of HBV-related traits. In this review, we discuss GWAS for persistence of HBV infection, antibody response to hepatitis B vaccine, and HBV-related advanced liver diseases. HBV persistence is associated with multiple genes with diverse roles in immune mechanisms. The strongest associations are found within the classical human leukocyte antigen (HLA) genes, highlighting the central role of antigen presentation in the immune response to HBV. Associated variants affect both epitope binding specificities and expression levels of HLA molecules. Several other susceptibility genes regulate the magnitude of adaptive immune responses, determining immunity vs tolerance. HBV persistence and nonresponse to vaccine share the same risk variants, implying overlapping genetic bases. On the other hand, the risk variants for HBV-related advanced liver diseases are largely different, suggesting different host-virus dynamics in acute vs chronic HBV infections. The findings of these GWAS are likely to pave the way for developing more effective preventive and therapeutic interventions by personalizing the management of HBV infection.
Collapse
Affiliation(s)
- Izzet Mehmet Akcay
- Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul 34469, Turkey
| | - Seyma Katrinli
- Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul 34469, Turkey
| | - Kamil Ozdil
- Department of Gastroenterology and Hepatology, Umraniye Teaching and Research Hospital, Istanbul 34764, Turkey
| | - Gizem Dinler Doganay
- Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul 34469, Turkey
| | - Levent Doganay
- Department of Gastroenterology and Hepatology, Umraniye Teaching and Research Hospital, Istanbul 34764, Turkey
| |
Collapse
|
|
14
|
Liao X, Yu L, Liu X, Han C, Yu T, Qin W, Yang C, Zhu G, Su H, Peng T. Genome-wide association pathway analysis to identify candidate single nucleotide polymorphisms and molecular pathways associated with TP53 expression status in HBV-related hepatocellular carcinoma. Cancer Manag Res 2018; 10:953-967. [PMID: 29760565 PMCID: PMC5937480 DOI: 10.2147/cmar.s163209] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background The aim of this investigation was to identify candidate single nucleotide polymorphisms (SNPs) and molecular pathways associated with tumor protein p53 (TP53) expression status in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), clarify their potential mechanisms, and generate SNP-to-gene to pathway hypothesis. Materials and methods Identify candidate Causal SNPs and Pathways (ICSNPathway) was used to perform pathway analysis based on the results of our previous genome-wide association study of TP53 expression status in 387 HBV-related HCC patients. Results Through the ICSNPathway analysis, we identified 18 candidate SNPs and 10 candidate pathways that are associated with TP53 expression status in HBV-related HCC. The strongest mechanism involved the modulation of major histocompatibility complex, class II, DP beta 1 (human leukocyte antigen [HLA]-DPB1-rs1042153), major histocompatibility complex, class II, DQ beta 1 (HLA-DQB1-rs1130399, HLA-DQB1-rs1049056, HLA-DQB1-rs1049059, and HLA-DQB1-rs1049060), and major histocompatibility complex, class II, DR beta 1 (HLA-DRB1-rs35445101). SNPs consequently affected regulatory roles in all the candidate pathways except hematopoietic cell lineage pathways. Association analysis using the GSE14520 data set, Gene Multiple Association Network Integration Algorithm, and Search Tool for the Retrieval of Interacting Genes/Proteins suggests that all genes of the candidate SNPs were associated with TP53. Survival analysis showed that the collagen type VI alpha 3 chain (COL6A3) rs111231885 and COL6A3-rs113155945 and COL6A3 block 4 CC haplotypes with TP53 negative status may have protective effects in HBV-related HCC patients after hepatectomy. Conclusion Our pathway analysis identified 18 candidate SNPs and 10 candidate pathways that were associated with TP53 expression status in HBV-related HCC. Among these candidate SNPs, the genetic variation of COL6A3 may be a potential prognostic biomarker of HBV-related HCC.
Collapse
Affiliation(s)
- Xiwen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Long Yu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Xiaoguang Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China.,Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China
| | - Chuangye Han
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Tingdong Yu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Wei Qin
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Chengkun Yang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Guangzhi Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Hao Su
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China
| |
Collapse
|
|
15
|
Lu WQ, Qiu JL, Huang ZL, Liu HY. Enhanced circulating transforming growth factor beta 1 is causally associated with an increased risk of hepatocellular carcinoma: a mendelian randomization meta-analysis. Oncotarget 2018; 7:84695-84704. [PMID: 27835897 PMCID: PMC5356692 DOI: 10.18632/oncotarget.13218] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2016] [Accepted: 10/25/2016] [Indexed: 02/07/2023] Open
Abstract
The aim of this study was to test the causal association between circulating transforming growth factor beta 1 (protein: TGF-β1 and coding gene: TGFB1) and hepatocellular carcinoma by choosing TGFB1 gene C-509T polymorphism as an instrument in a Mendelian randomization (MR) meta-analysis. Ten English articles were identified for analysis. Two authors independently assessed each article and abstracted relevant data. Odds ratio (OR) and weighted mean difference (WMD) with 95% confidence interval (CI) were synthesized under a random-effects model. Overall, the association of C-509T polymorphism with hepatocellular carcinoma was negative, but its association with circulating TGF-β1 was statistically significant, with a higher concentration observed in carriers of the -509TT genotype (WMD, 95% CI, P: 1.72, 0.67–2.78, 0.001) and -509TT/-509TC genotypes (WMD, 95% CI, P: 0.98, 0.43–1.53, < 0.001). In subgroup analysis, C-509T polymorphism was significantly associated with hepatocellular carcinoma in population-based studies under homozygous-genotype (OR, 95% CI, P: 1.74, 1.08–2.80, 0.023) and dominant (OR, 95% CI, P: 1.48, 1.01–2.17, 0.047) models. Further MR analysis indicated that per unit increase in circulating TGF-β1 was significantly associated with a 38% (95% CI: 1.03–4.65) and 49% (95% CI: 1.01–6.06) increased risk of hepatocellular carcinoma under homozygous-genotype and dominant models, respectively. Conclusively, based on a MR meta-analysis, our findings suggest that enhanced circulating TGF-β1 is causally associated with an increased risk of hepatocellular carcinoma.
Collapse
Affiliation(s)
- Wei-Qun Lu
- Department of Gastrointestinal Tumor Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Ji-Liang Qiu
- Department of Gastrointestinal Tumor Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Zhi-Liang Huang
- Department of Gastrointestinal Tumor Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Hai-Ying Liu
- Department of Gastrointestinal Tumor Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China
| |
Collapse
|
|
16
|
Okada Y, Uno N, Sato S, Mori S, Sasaki D, Kaku N, Kosai K, Morinaga Y, Hasegawa H, Yanagihara K. Strong influence of human leukocyte antigen-DP variants on response to hepatitis B vaccine in a Japanese population. Vaccine 2017; 35:5662-5665. [PMID: 28882445 DOI: 10.1016/j.vaccine.2017.08.045] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Revised: 08/14/2017] [Accepted: 08/19/2017] [Indexed: 12/17/2022]
Abstract
Genome-wide association studies (GWASs) have reported that human leukocyte antigen (HLA) variants are associated with chronic hepatitis B, spontaneous hepatitis B virus (HBV) clearance, and response to hepatitis B vaccine. Single nucleotide polymorphisms (SNPs) in HLA-DP (rs9277535 and rs3077) and HLA-DQ (rs2856718 and rs7453920) have been repeatedly associated with chronic hepatitis B and spontaneous HBV clearance. However, the data on the SNPs associated with response to hepatitis B vaccine are inconclusive. The objective of this study was to determine whether these four HLA SNPs that have been identified as risk loci for chronic HBV infection are associated with response to hepatitis B vaccine in a Japanese population. We enrolled 278 medical students who received hepatitis B vaccination and measured anti-hepatitis B surface (HBs) antibody titers 1month after a three-dose vaccination series. We found that rs9277535 and rs3077 in HLA-DP were strongly associated with response to hepatitis B vaccine (odds ratio [OR]=0.31 and 0.32, P=0.004 and 0.010, respectively). These two SNPs were significantly associated with anti-HBs titers in an allele-dependent manner. On the other hand, rs2856718 and rs7453920 in HLA-DQ were not associated with response to hepatitis B vaccine. These results indicate that rs9277535 and rs3077 in HLA-DP are the major determinants of response to hepatitis B vaccine, whereas rs2856718 and rs7453920 in HLA-DQ have little effect on the immune response to hepatitis B vaccine.
Collapse
Affiliation(s)
- Yuya Okada
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
| | - Naoki Uno
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
| | - Shuntaro Sato
- Clinical Research Center, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
| | - Sayaka Mori
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
| | - Daisuke Sasaki
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
| | - Norihito Kaku
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
| | - Kosuke Kosai
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
| | - Yoshitomo Morinaga
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
| | - Hiroo Hasegawa
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
| | - Katsunori Yanagihara
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
| |
Collapse
|
|
17
|
Li Y, Huang Q, Tang JT, Wei TT, Yan L, Yang ZQ, Bai YJ, Wang LL, Shi YY. Correlation of HLA-DP/DQ polymorphisms with transplant etiologies and prognosis in liver transplant recipients. Medicine (Baltimore) 2017; 96:e7205. [PMID: 28640108 PMCID: PMC5484216 DOI: 10.1097/md.0000000000007205] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Previous study has identified that the genetic variants in the human leukocyte antigen (HLA)-DP/DQ region were strongly associated with hepatitis B virus (HBV) infection. But their roles in liver function recovery after hepatic transplantation were still obscure. This study aimed to investigate whether HLA-DP/DQ polymorphisms were associated with post-transplant etiologies and prognosis in Chinese liver transplant recipients.A total of 144 liver transplant recipients were enrolled, which were divided into 2 groups according to the transplant etiology: HBV-related disease and non-HBV-related disease. HBV-related disease includes 3 subgroups: liver cirrhosis, hepatocellular carcinoma, and progressive HBV hepatitis. Three single-nucleotide polymorphisms HLA-DP (rs3077 and rs9277535) and HLA-DQ (rs7453920) were studied in all recipients by high-resolution melting curve analysis. Liver function indices (albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, direct bilirubin, total bilirubin) and coagulation indices (prothrombin time, platelet, international normalized ratio, fibrinogen) were routinely tested. After transplant, 10 recipients who were positive for HBsAg or with elevation in HBV virus load were regarded as HBV recurrence.No significant association of HLA-DP/DQ polymorphisms with HBV recurrence or transplant etiology was observed (P < .05). Recipients with HLA-DQ (rs7453920) AG and AA genotype had lower direct bilirubin levels than GG genotype individuals, especially on the 14th day after surgery (17.80 vs. 5.35, P = .038). Patients with A alleles displayed earlier liver function recovery than patients with G alleles (7 vs. 6 months). No significant correlation was shown in HLA-DP rs3077 and rs9277535 with HBV infection or liver function recovery (P < .05).Our study concluded that HLA-DP (rs3077 and rs9277535) and HLA-DQ (rs7453920) were not significantly associated with HBV recurrence or HBV susceptibility, but HLA-DQ rs7453920 was related to prognosis of liver transplant recipients. HLA-DQ rs7453920 A might be used as an indicator of earlier recovery and better prognosis after transplantation.
Collapse
Affiliation(s)
- Yi Li
- Department of Laboratory Medicine, Division of Clinical Immunology, West China Hospital of Sichuan University
| | - Qian Huang
- West China School of Medicine, Sichuan University
| | - Jiang-Tao Tang
- Department of Laboratory Medicine, Division of Clinical Immunology, West China Hospital of Sichuan University
| | | | - Lin Yan
- Department of Laboratory Medicine, Division of Clinical Immunology, West China Hospital of Sichuan University
| | | | - Yang-Juan Bai
- Department of Laboratory Medicine, Division of Clinical Immunology, West China Hospital of Sichuan University
| | - Lan-Lan Wang
- Department of Laboratory Medicine, Division of Clinical Immunology, West China Hospital of Sichuan University
| | - Yun-Ying Shi
- Department of Nephrology, West China Hospital of Sichuan University, Chengdu, China
| |
Collapse
|
|
18
|
Quantitative assessment of the effect of pre-gestational diabetes and risk of adverse maternal, perinatal and neonatal outcomes. Oncotarget 2017; 8:61048-61056. [PMID: 28977845 PMCID: PMC5617405 DOI: 10.18632/oncotarget.17824] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Accepted: 04/05/2017] [Indexed: 01/11/2023] Open
Abstract
Pregnancies complicated by pre-gestational diabetes (PGD) are associated with a higher rate of adverse outcomes, including an increased rage of preterm delivery, pregnancy-induced hypertension, pre-eclampsia, caesarean section, perinatal mortality, stillbirth, shoulder dystocia, macrosomia, small for gestational age, large for gestational age, low birth weight, neonatal hypoglycemia, neonatal death, low Apgar score, NICU admission, jaundice and respiratory distress. In the past two decades, numerous reports have been published regarding associations between PGD and risk of adverse outcomes. However, study results are inconsistent. To provide a synopsis of the current understanding of PGD for risk of adverse pregnancy outcomes, a random-effects meta-analysis over 40 million subjects from 100 studies was performed to calculate the pooled ORs. Potential sources of heterogeneity were systematically explored by multiple strata analyses and meta-regression. Overall, PGD were significantly associated with increased risk of preterm delivery (OR=3.48), LGA (OR=3.90), perinatal mortality (OR=3.39), stillbirth (OR=3.52), pre-eclampsia (OR=3.48), caesarean section (OR=3.52), NICU admission (OR=3.92), and neonatal hypoglycemia (OR=26.62). Significant results were also observed for 7 adverse outcomes with OR range from 1.54 to 2.82, while no association was found for SGA and respiratory distress after Bonferroni correction. We found that women with T1DM had higher risks for most of adverse pregnancy outcomes compared with women with T2DM. When stratified by study design, sample size, type of diabetes, geographic region, and study quality, significant associations remains. Our findings demonstrated that PGD is a strong risk-conferring factor for adverse maternal, perinatal and neonatal outcomes.
Collapse
|
|
19
|
Relationship between HLA-DQ Gene Polymorphism and Hepatitis B Virus Infection. BIOMED RESEARCH INTERNATIONAL 2017; 2017:9679843. [PMID: 28512640 PMCID: PMC5420426 DOI: 10.1155/2017/9679843] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2016] [Revised: 03/21/2017] [Accepted: 04/02/2017] [Indexed: 12/24/2022]
Abstract
Hepatitis B virus (HBV) infection is the predominant risk factor for chronic hepatitis B (CHB). The association between HBV infection and human leukocyte antigen- (HLA-) DQ polymorphism (rs2856718 and rs7453920) has been demonstrated in other studies; however, the results were controversial or inconclusive. Therefore, to derive a more precise estimation of the association, a meta-analysis was performed. Crude odds ratios (ORs) and their 95% confidence intervals (CIs) were used to assess the strength of association between HLA-DQ polymorphism (rs2856718 and rs7453920) and HBV infection risk. A total of 11 articles were used to evaluate the effect of the two polymorphisms on risk of HBV infection. The pooled data showed that HLA-DQ rs2856718-G polymorphism showed protection against HBV infection, and rs2856718-A was a risk factor for chronic HBV infection. The pooled risk estimates indicated that HLA-DQ rs7453920-A polymorphism was associated with decreased risk of HBV infection, and rs7453920-G serves as a risk factor in HBV infection. However, these stratified analyses were lacking credibility due to the limitation of correlational study numbers; further investigation on a large population and different ethnicities is warranted.
Collapse
|
|
20
|
Zhang J, Zhan W, Yang B, Tian A, Chen L, Liao Y, Wu Y, Cai B, Wang L. Genetic Polymorphisms of rs3077 and rs9277535 in HLA-DP associated with Systemic lupus erythematosus in a Chinese population. Sci Rep 2017; 7:39757. [PMID: 28094303 PMCID: PMC5240340 DOI: 10.1038/srep39757] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Accepted: 11/28/2016] [Indexed: 02/05/2023] Open
Abstract
Although the SLE risk gene loci of HLA-DR and HLA-DQ within the major histocompatibility complex (MHC) region has been gradually revealed by recent Genome-Wide Association studies (GWAS), the association of HLA-DP polymorphisms with SLE was minimally reported. Considering that the variants in rs3077 and rs9277535 in the HLA-DP region could influence the immune response by affecting antigen presentation of HLA class II molecules to CD4+ T cells, the present study aimed to explore the role of HLA-DP polymorphisms in SLE. In total, samples from 335 SLE patients and 635 healthy controls were collected and genotyped by a polymerase chain reaction-high resolution melting (PCR-HRM) assay. A significant positive correlation was observed between the SNP rs3077, rs9277535 of HLA-DP and SLE susceptibility (rs3077, OR = 0.74, 95%CI = 0.60-0.91, P = 0.004; rs9277535, OR = 0.72, 95%CI = 0.59-0.88, P = 0.001). Rs3077 polymorphism was corelated to IL-17, INF-γ and cutaneous vasculitis (P = 0.037, P = 0.020 and P = 0.006, respectively). Additionally, rs3077 AA genotype carriers showed lower concentration of inflammatory cytokines and lower cutaneous vasculitis incidence than did the other two genotype. No significant association was observed between rs9277535 and cytokines or any clinical features. In conclusion, HLA-DP polymorphisms (rs3077 and rs9277535) were associated with SLE susceptibility and the levels of some inflammatory cytokines in SLE patients.
Collapse
Affiliation(s)
- Junlong Zhang
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Wenli Zhan
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Bin Yang
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Anning Tian
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Lin Chen
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Yun Liao
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Yongkang Wu
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Bei Cai
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Lanlan Wang
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| |
Collapse
|
|
21
|
Cholecystectomy is associated with higher risk of early recurrence and poorer survival after curative resection for early stage hepatocellular carcinoma. Sci Rep 2016; 6:28229. [PMID: 27320390 PMCID: PMC4913319 DOI: 10.1038/srep28229] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Accepted: 05/31/2016] [Indexed: 02/07/2023] Open
Abstract
Although cholecystectomy has been reported to be associated with increased risk of developing hepatocellular carcinoma (HCC), the association between cholecystectomy and prognosis of HCC patients underwent curative resection has never been examined. Through retrospective analysis of the data of 3933 patients underwent curative resection for HCC, we found that cholecystectomy was an independent prognostic factor for recurrence-free survival (RFS) of patients at early stage (BCLC stage 0/A) (p = 0.020, HR: 1.29, 95% CI: 1.04-1.59), and the 1-, 3-, 5-year RFS rates for patients at early stage were significantly worse in cholecystectomy group than in non-cholecystectomy group (80.5%, 61.8%, 52.0% vs 88.2%, 68.8%, 56.8%, p = 0.033). The early recurrence rate of cholecystectomy group was significantly higher than that of non-cholecystectomy group for patients at early stage (59/47 vs 236/333, p = 0.007), but not for patients at advanced stage (BCLC stage C) (p = 0.194). Multivariate analyses showed that cholecystectomy was an independent risk factor for early recurrence (p = 0.005, HR: 1.52, 95% CI: 1.13-2.03) of early stage HCC, but not for late recurrence (p = 0.959). In conclusion, cholecystectomy is an independent predictor for early recurrence and is associated with poorer RFS of early stage HCC. Removal of normal gallbladder during HCC resection may be avoided for early stage patients.
Collapse
|
|
22
|
Wang L, Zou ZQ, Wang K. Clinical Relevance of HLA Gene Variants in HBV Infection. J Immunol Res 2016; 2016:9069375. [PMID: 27243039 PMCID: PMC4875979 DOI: 10.1155/2016/9069375] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2016] [Accepted: 04/14/2016] [Indexed: 01/01/2023] Open
Abstract
Host gene variants may influence the natural history of hepatitis B virus (HBV) infection. The human leukocyte antigen (HLA) system, the major histocompatibility complex (MHC) in humans, is one of the most important host factors that are correlated with the clinical course of HBV infection. Genome-wide association studies (GWASs) have shown that single nucleotide polymorphisms (SNPs) near certain HLA gene loci are strongly associated with not only persistent HBV infection but also spontaneous HBV clearance and seroconversion, disease progression, and the development of liver cirrhosis and HBV-related hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB). These variations also influence the efficacy of interferon (IFN) and nucleot(s)ide analogue (NA) treatment and response to HBV vaccines. Meanwhile, discrepant conclusions were reached with different patient cohorts. It is therefore essential to identify the associations of specific HLA allele variants with disease progression and viral clearance in chronic HBV infection among different ethnic populations. A better understanding of HLA polymorphism relevance in HBV infection outcome would enable us to elucidate the roles of HLA SNPs in the pathogenesis and clearance of HBV in different areas and ethnic groups, to improve strategies for the prevention and treatment of chronic HBV infection.
Collapse
Affiliation(s)
- Li Wang
- Infectious Disease Hospital of Yantai, 62 Huanshan Road, Zhifu District, Yantai, Shandong 264001, China
| | - Zhi-Qiang Zou
- Infectious Disease Hospital of Yantai, 62 Huanshan Road, Zhifu District, Yantai, Shandong 264001, China
| | - Kai Wang
- Hepatology Department, Qilu Hospital of Shandong University, 44 Wenhua West Road, Lixia District, Jinan, Shandong 250012, China
| |
Collapse
|