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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Association between human leukocyte antigen gene polymorphisms and multiple EPIYA-C repeats in gastrointestinal disorders
Suat Saribas, Suleyman Demiryas, Erkan Yilmaz, Omer Uysal, Nuray Kepil, Mehmet Demirci, Reyhan Caliskan, Harika Oyku Dinc, Seher Akkus, Nesrin Gareayaghi, Sahra Kirmusaoglu, Dogukan Ozbey, Hrisi B Tokman, Serdar S Koksal, Ihsan Tasci, Bekir Kocazeybek
Suat Saribas, Reyhan Caliskan, Harika Oyku Dinc, Seher Akkus, Dogukan Ozbey, Hrisi B Tokman, Bekir Kocazeybek, Department of Medical Microbiology, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul 34098, Turkey
Suleyman Demiryas, Ihsan Tasci, Department of General Surgery, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul 34098, Turkey
Erkan Yilmaz, Department of Organ Transplantation, HLA Laboratory, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul 34098, Turkey
Omer Uysal, Deparment of Biostatistics, Medical School of Bezmialem Vakif University, Istanbul 34093, Turkey
Nuray Kepil, Department of Pathology, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul 34098, Turkey
Mehmet Demirci, Department of Medical Microbiology, Beykent University Medical Faculty, Istanbul 34520, Turkey
Nesrin Gareayaghi, Center for Blood, Istanbul Sisli Hamidiye Etfal Training and Research Hospital, University of Health Sciences, Istanbul 34360, Turkey
Sahra Kirmusaoglu, Department of Molecular Biology and Genetics, T.C. Halic University, Faculty of Arts & Sciences, Istanbul 34381, Turkey
Serdar S Koksal, Department of Public Health, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul 34098, Turkey
Author contributions: Saribas S, Demiryas S, Ozbey D and Kocazeybek B designed and coordinated the study; Caliskan R, Tasci I, Demirci M, Dinc HO and Kirmusaoglu S performed the experiments, acquired and analyzed data;Yilmaz E, Kepil N,Uysal O, Akkus S, Gareayaghi N interpreted the data; Koksal SS, Tokman HB, Saribas S, Kocazeybek B wrote the manuscript; all authors approved the final version of the article.
Supported by the Istanbul University Research Fund, No. 45151.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the Istanbul University.
Informed consent statement: Informed written consent was obtained from the patients.
Conflict-of-interest statement: The authors have nothing to disclose.
Data sharing statement: No additional data are available.
STROBE statement: The guidelines of the STROBE Statement have been adopted.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Bekir Kocazeybek, PhD, Full Professor, Professor, Department of Medical Microbiology, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Cerrahpasa Street, Istanbul 34098, Turkey.
bzeybek@istanbul.edu.tr
Received: March 12, 2020
Peer-review started: March 12, 2020
First decision: May 15, 2020
Revised: July 2, 2020
Accepted: August 20, 2020
Article in press: August 20, 2020
Published online: August 28, 2020
Processing time: 168 Days and 17.5 Hours
BACKGROUND
Polymorphisms of human leukocyte antigen (HLA) genes are suggested to increase the risk of gastric cancer (GC).
AIM
To investigate the HLA allele frequencies of patients with GC relative to a control group in terms of CagA+ multiple (≥ 2) EPIYA-C repeats.
METHODS
The patient group comprised 94 patients [44 GC and 50 duodenal ulcer (DU) patients], and the control group comprised 86 individuals [(50 non-ulcer dyspepsia patients and 36 people with asymptomatic Helicobacter pylori (H. pylori)]. Polymerase chain reaction was performed for the amplification of the H. pylori cagA gene and typing of EPIYA motifs. HLA sequence-specific oligonucleotide (SSO) typing was performed using Lifecodes SSO typing kits (HLA-A, HLA-B HLA-C, HLA-DRB1, and HLA-DQA1-B1 kits).
RESULTS
The comparison of GC cases in terms of CagA+ multiple (≥ 2) EPIYA-C repeats showed that only the HLA-DQB1*06 allele [odds ratio (OR): 0.37, P = 0.036] was significantly lower, but significance was lost after correction (Pc = 0.1845). The HLA-DQA1*01 allele had a high ratio in GC cases with multiple EPIYA-C repeats, but this was not significant in the univariate analysis. We compared allele frequencies in the DU cases alone and in GC and DU cases together using the same criterion, and none of the HLA alleles were significantly associated with GC or DU. Also, none of the alleles were detected as independent risk factors after the multivariate analysis. On the other hand, in a multivariate logistic regression with no discriminative criterion, HLA-DQA1*01 (OR = 1.848), HLA-DQB1*06 (OR = 1.821) and HLA-A*02 (OR = 1.579) alleles were detected as independent risk factors for GC and DU.
CONCLUSION
None of the HLA alleles were detected as independent risk factors in terms of CagA+ multiple EPIYA-C repeats. However, HLA-DQA1*01, HLA-DQB1*0601, and HLA-A*2 were independent risk factors with no criterion in the multivariate analysis. We suggest that the association of these alleles with gastric malignancies is not specifically related to cagA and multiple EPIYA C repeats.
Core tip: The development of gastric cancer (GC) is suggested to be related to the interactions of bacterial virulence and host genetic factors with the immune response of the host. The effects of polymorphisms in the human leukocyte antigen (HLA) gene may regulate the degree of the inflammatory response of the host leading to the gastric malignancies. We could not detect any prominent HLA alleles between the patient and control groups in terms of CagA+ multiple (≥ 2) EPIYA-C repeat numbers. HLA-DQA1*01, HLA-DQB1*06, and HLA-A*02 were detected as independent risk factors for the risk of GC and duodenal ulcer with no criterion in multivariate analyses. We suggest that the association of these alleles with gastric malignancies is not specifically related to cagA and multiple EPIYA C repeats.
