While persistence or resolution of HBV infection may be affected by a variety of factors, including viral, environmental and host factors, family or twin studies have suggested that host genetic constitution is also an important factor which influences chronicity of HBV infection [2], [3]. Many host genetic variations, including genes coding inhibitor supplier for cytokines such as interferon-gamma and tumor necrosis factors [4], estrogen receptor alpha [5], vitamin D receptor [6], mannose-binding protein [7], cytotoxic T-lymphocyte antigen 4 (CTLA-4) [8] and human leukocyte antigen (HLA) [9], [10], [11], [12], have been suggested to influence chronicity or clearance of HBV infection.

In particular, single nucleotide polymorphisms (SNPs) near the CTLA-4, genes coding for an inhibitory receptor expressed by T-lymphocytes, and near the HLA-DR13 locus, coding for component of the major histocompatibility complex class II cell surface receptors, have been studied in several case-control studies for their association with HBV infection in different populations [8], [9], [10], [11], [12]. However, these candidate gene studies were not conducted on a large scale genome-wide approach. Several genome-wide association studies (GWAS) have been performed with large cohorts to study the association of genetic variations with HBV infection. These GWAS studies did not find a strong association between HBV infection and those previously identified candidate HBV-associated SNPs. These GWAS studies demonstrated that certain SNPs near the HLA-DP loci, are associated with persistent HBV infection [13], [14], [15].

In a pioneering GWAS study with 786 Japanese chronic HBV carriers and 2,201 controls, Kamatani and colleagues have identified an association between chronic hepatitis B and 11 SNPs in the HLA-DP region, two of which, namely rs3077 and rs9277535, were further validated in three additional Japanese and Thai cohorts [13]. The association between these HLA-DP SNPs with chronicity and/or clearance Anacetrapib of HBV infection was further confirmed by two other GWAS studies, one with 2,667 Japanese chronic HBV carriers and 6,496 controls by the same group [14] and one with 181 Japanese chronic HBV carries, 184 healthy controls, and 185 individuals with natural clearance of HBV [15]. The association of some of these HLA-DP SNPs with HBV infection has been verified in many studies, but the association differs between studies in different population cohorts, and more SNPs are yet to be identified [16], [17], [18], [19], [20], [21]. HLA-DP molecules, belonging to HLA class II, are involved in antigen presentation to CD4+ T helper cells.