Retrospective Study
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World J Gastroenterol. Jul 7, 2014; 20(25): 8179-8186
Published online Jul 7, 2014. doi: 10.3748/wjg.v20.i25.8179
Association of human leukocyte antigen DQB1 and DRB1 alleles with chronic hepatitis B
Levent Doganay, Arta Fejzullahu, Seyma Katrinli, Feruze Yilmaz Enc, Oguzhan Ozturk, Yasar Colak, Celal Ulasoglu, Ilyas Tuncer, Gizem Dinler Doganay
Levent Doganay, Feruze Yilmaz Enc, Yasar Colak, Celal Ulasoglu, Ilyas Tuncer, Department of Gastroenterology, Goztepe Teaching and Research Hospital, Medeniyet University, Istanbul 34722, Turkey
Levent Doganay, Oguzhan Ozturk, Department of Gastroenterology, Umraniye Teaching and Research Hospital, Istanbul 34760, Turkey
Arta Fejzullahu, Seyma Katrinli, Gizem Dinler Doganay, Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul 34469, Turkey
Author contributions: Doganay L and Dinler Doganay G equally contributed to this study; Doganay L, Dinler Doganay G, Fejzullahu A, Katrinli S and Tuncer I designed the research; Doganay L, Yilmaz Enc F, Ozturk O, Colak Y and Ulasoglu C collected the clinical data; Doganay L and Yilmaz Enc F collected the patients’ specimens; Dinler Doganay G, Fejzullahu A and Katrinli S performed the research; Doganay L and Dinler Doganay G analyzed the data; Doganay L and Dinler Doganay G wrote the paper.
Supported by Internal research funds of Istanbul Technical University, No. 36403
Correspondence to: Gizem Dinler Doganay, PhD, Associate Professor, Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul 34469, Turkey. gddoganay@itu.edu.tr
Telephone: +90-212-2857249 Fax: +90-212-2856386
Received: December 12, 2013
Revised: February 17, 2014
Accepted: April 1, 2014
Published online: July 7, 2014
Processing time: 202 Days and 21.1 Hours
Abstract

AIM: To investigate the effect of human leukocyte antigen (HLA) DRB1 and DQB1 alleles on the inactive and advanced stages of chronic hepatitis B.

METHODS: Patient records at a single institution’s hepatology clinic were reviewed. Demographic data, laboratory results, endoscopy results, virological parameters, biopsy scores and treatment statuses were recorded. In total, 355 patients were eligible for the study, of whom 226 (63.7%) were male. Overall, 82 (23.1%) were hepatitis B early antigen (HBeAg) positive, 87 (24.5%) had cirrhosis, and 66 (18.6%) had inactive disease. The presence of DQB1 and DRB1 alleles was determined by polymerase chain reaction with sequence-specific primers. The distribution of the genotyped alleles among patients with cirrhosis and patients with chronic active hepatitis was analyzed.

RESULTS: The most frequent HLA DQB1 allele was DQB1*03:01 (48.2%), and the most frequent HLA DRB1 allele was DRB1*13/14 (51.8%). DQB1*05:01 was more frequent in patients with active disease than in inactive patients (27% vs 9.1%; P = 0.002, Pc = 0.026). DRB1*07 was rare in patients with cirrhosis compared with non-cirrhotics (3.4% vs 16%; P = 0.002, Pc = 0.022). Older age (P < 0.001) and male gender (P = 0.008) were the other factors that affected the presence of cirrhosis. In a multivariate logistic regression analysis, DRB1*07 remained a significant negative predictor of cirrhosis (P = 0.015). A bioinformatics analysis revealed that a polymorphic amino acid sequence in DRB1*07 may alter interaction with the T-cell recognition site.

CONCLUSION: This study demonstrates that HLA alleles may influence cirrhosis development and disease activity in Turkish chronic hepatitis B patients.

Keywords: Chronic active hepatitis; Cirrhosis; Hepatitis B; Human leukocyte antigen DQ; Human leukocyte antigen DR

Core tip: Chronic hepatitis B is a major health problem worldwide. Recent genome-wide association studies revealed a significant association between the human leukocyte antigen (HLA) class II region and chronic hepatitis B. In the present study, we genotyped HLA DQB1 and DRB1 alleles in 355 chronic hepatitis B patients and investigated the effects of the HLA alleles on disease activity and cirrhosis development. We found that DQB1*05:01 was a risk factor for chronic active hepatitis and that DRB1*07 was a protective factor against cirrhosis. A bioinformatics analysis revealed that DRB1*07 might be associated with a hypoimmune response.