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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
ARTICLE HIGHLIGHTS
Research background
The development of gastric cancer (GC) is suggested to be related to the interactions between bacterial virulence factors, host genetic factors such as the human leukocyte antigen (HLA) gene, the immune response of the host, and environmental factors. Some of the host factors may be polymorphisms in the host genes such as HLA genes, which regulate the strength of the inflammatory response and influence the probability of a specific clinical outcome.
Research motivation
We seek to determine which HLA class I and II alleles differ in gastrointestinal pathologies such as GC and duodenal ulcer (DU) in Turkey.
Research objectives
We investigated the allele frequencies of HLA class I and II in a patient group [Helicobacter pylori (H. pylori)-positive GC and DU patients] and compared the results to a control group (H. pylori-positive non-ulcer dyspepsia patients and asymptomatic individuals with H. pylori) in terms of CagA+ multiple (≥ 2) EPIYA-C repeats for the first time in a Turkish population.
Research methods
In this case-control study, amplification of the H. pylori cagA gene and typing of EPIYA motifs were performed by PCR. HLA allele types were identified by sequence-specific oligonucleotide typing kits (HLA-A, HLA-B HLA-C, HLA-DRB1, and HLA-DQA1/B1 kits).
Research results
None of the alleles were detected as independent risk factors after multivariate analysis in terms of CagA+ multiple (≥ 2) EPIYA-C repeats. On the other hand, in a multivariate logistic regression with no discriminative criterion, HLA-DQA1*01 [odds ratio (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.
Research conclusions
We suggest that the association of these alleles with gastric malignancies is not specifically related to cagA and multiple EPIYA C repeats.
Research perspectives
Specific HLA alleles maybe related to the gastric malignancies and could be for the indication of GCs in order to scan populations before the development of GC. The alleles may also be cost-effective to find individuals with a higher risk for GC development.
