Case Control Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2024; 30(46): 4880-4903
Published online Dec 14, 2024. doi: 10.3748/wjg.v30.i46.4880
Multi-clustering study on the association between human leukocyte antigen-DP-DQ and hepatitis B virus-related hepatocellular carcinoma and cirrhosis in Viet Nam
Thuy Thu Nguyen, Tu Cam Ho, Huong Thi Thu Bui, Van-Khanh Tran, Tue Trong Nguyen
Thuy Thu Nguyen, Tu Cam Ho, Van-Khanh Tran, Center for Gene and Protein Research, Hanoi Medical University, Hanoi 116177, Viet Nam
Tu Cam Ho, Institute of Virology, TUM School of Medicine, Technical University of Munich, Munich 81675, Germany
Huong Thi Thu Bui, Department of Biochemistry, Thai Nguyen University of Medicine and Pharmacy, Thai Nguyen 251540, Viet Nam
Tue Trong Nguyen, Medical Technology Department, Hanoi Medical University, Hanoi 116177, Viet Nam
Tue Trong Nguyen, Clinical Laboratory, Hanoi Medical University Hospital, Hanoi 116177, Viet Nam
Author contributions: Nguyen TT and Nguyen TT designed the present study; Nguyen TT received the grant for the study; Nguyen TT, Nguyen TT, Ho TC and Bui HTT performed the data collection and the experiments; Ho TC performed the data mining and hierarchical clustering analysis study; Nguyen TT, Ho TC and Nguyen TT wrote the main manuscript; Tran VK revised the manuscript. All authors read and approved the final manuscript.
Supported by National Foundation for Science and Technology Development (NAFOSTED)-Ministry of Science and Technology, Viet Nam, No. 108.02-2019.307.
Institutional review board statement: The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Hanoi Medical University (No. HMUIRB109). Written informed consent was obtained from the subjects regarding the use of the samples and information for research purposes.
Informed consent statement: All study participants, or their legal guardians, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: No conflict of interest has been declared by any of the authors impacting on the work presented in this manuscript.
Data sharing statement: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. We, however, cannot provide personal information or data containing patient identification in any form.
STROBE statement: The authors have read the STROBE Statement-a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Tue Trong Nguyen, DPhil, Academic Research, Chief Technician, Research Scientist, Researcher, Medical Technology Department, Hanoi Medical University, No. 1 Ton That Tung Street, Dong Da District, Hanoi 116177, Viet Nam. trongtue@hmu.edu.vn
Received: March 7, 2024
Revised: September 4, 2024
Accepted: October 16, 2024
Published online: December 14, 2024
Processing time: 259 Days and 0.7 Hours
Abstract
BACKGROUND

Human leukocyte antigen (HLA) class II molecules are cell surface receptor proteins found on antigen-presenting cells. Polymorphisms and mutations in the HLA gene can affect the immune system and the progression of hepatitis B.

AIM

To study the relation between rs2856718 of HLA-DQ, rs3077, and rs9277535 of HLA-DP, hepatitis B virus (HBV)-related cirrhosis, and hepatocellular carcinoma (HCC).

METHODS

In this case-control study, the genotypes of these single nucleotide polymorphisms (SNPs) were screened in 315 healthy controls, 471 chronic hepatitis B patients, 250 patients with HBV-related liver cirrhosis, and 251 patients with HCC using TaqMan real-time PCR. We conducted Hardy-Weinberg equilibrium and linkage disequilibrium tests on the genotype distributions of rs2856718, rs3077, and rs9277535 before hierarchical clustering analysis to build the complex interaction between the markers in each patient group.

RESULTS

The physical distance separating these SNPs was 29816 kB with the disequilibrium (D’) values ranging from 0.07 to 0.34. The close linkage between rs3077 and rs9277535 was attributed to a distance of 21 kB. The D’ value decreased from moderate in the healthy control group (D’ = 0.50, P < 0.05) to weak in the hepatic disease group (D’ < 0.3, P < 0.05). In a combination of the three variants rs2856718, rs3077, and rs9277535, the A allele decreased hepatic disease risk [A-A-A haplotype, risk ratio (RR) = 0.44 (0.14; 1.37), P < 0.05]. The G allele had the opposite effect [G-A/G-G haplotype, RR = 1.12 (1.02; 1.23), P < 0.05]. In liver cancer cases, the A-A-A/G haplotype increased the risk of HCC by 1.58 (P < 0.05).

CONCLUSION

Rs9277535 affects liver fibrosis progression due to HBV infection, while rs3077 is associated with a risk of HBV-related HCC. The link between rs2856718, rs3077, and rs9277535 and disease risk was determined using a multi-clustering analysis.

Keywords: Human leukocyte antigen; Multi-clustering study; Hepatitis B virus; Hepatocellular carcinoma; Cirrhosis

Core Tip: A significant correlation was observed between Human leukocyte antigen (HLA)-DP-DQ polymorphisms and the risk of hepatitis B virus (HBV)-related liver cirrhosis (LC) and hepatocellular carcinoma (HCC). In this study, individuals with the HLA-DP and HLA-DQ genotypes were found to have a higher prevalence of LC and HCC. The hypothesis that HLA polymorphisms play a crucial role in the progression of HBV-related liver diseases has been confirmed. Specific HLA-DP and HLA-DQ alleles were associated with the risk of HBV-related LC and HCC. By delving into the genetic underpinnings of these diseases, we highlight the potential for developing personalized medical approaches and targeted therapies for affected individuals.