Association between chronic hepatitis B virus infection and HLA-DP gene polymorphisms in the Turkish population

Abstract

Aim: Hepatitis B virus (HBV) affects approximately 360 million people worldwide. 10-15% of patients with chronic HBV develop liver cirrhosis (LC), liver failure and hepatocellular carcinoma (HCC). Chronic HBV infection or HBV clearance is influenced by both viral and host factors. In genome-wide association studies (GWAS), the human leukocyte antigen (HLA) gene polymorphisms rs3077 and rs9277535 were identified to be associated with chronic hepatitis B. HLA genes have been linked to immune response to infectious agents. Genetic variants in HLA genes influence HLA mRNA expression which might also affect antigen presentation. We evaluated the association between HLA gene polymorphisms and the risk for persistent HBV infection.

Methods: In the current study, HLA gene polymorphisms were investigated in a case-control study of 294 chronic HBV patients and 234 persons with HBV natural clearance by using a real-time polymerase chain reaction (RT-PCR).

Results: The results showed that rs9277535 allele frequency is associated with HBV infection in the Turkish subjects examined (P=0.048). However, no association was found for rs3077. Additionally, the AG haplotype block showed a protective effect against the risk of persistent HBV infection (for the rs3077A/rs9277535G, OR=0.52; 95% 0.34-0.80, P=0.003).

Conclusions: Our results, for the first time, demonstrate that HLA-DPB1 gene rs9277535A allele has a major effect on the risk of persistent HBV infection. We suggest that further independent studies are necessary to clarify the association of these polymorphisms with persistence or natural clearance of HBV infection in Caucasian populations.

Keywords: HBV clearance; HLA polymorphism; rs3077; rs9277535.