New Susceptibility and Resistance HLA-DP Alleles to HBV-Related Diseases Identified by a Trans-Ethnic Association Study in Asia

<div><p>Previous studies have revealed the association between SNPs located on human leukocyte antigen (<i>HLA</i>) class II genes, including <i>HLA-DP</i> and <i>HLA-DQ</i>, and chronic hepatitis B virus (HBV) infection, mainly in Asian populations. <i>HLA-DP</i> alleles or haplotypes associated with chronic HBV infection or disease progression have not been fully identified in Asian populations. We performed trans-ethnic association analyses of <i>HLA-DPA1</i>, <i>HLA-DPB1</i> alleles and haplotypes with hepatitis B virus infection and disease progression among Asian populations comprising Japanese, Korean, Hong Kong, and Thai subjects. To assess the association between <i>HLA-DP</i> and chronic HBV infection and disease progression, we conducted high-resolution (4-digit) <i>HLA-DPA1</i> and <i>HLA-DPB1</i> genotyping in a total of 3,167 samples, including HBV patients, HBV-resolved individuals and healthy controls. Trans-ethnic association analyses among Asian populations identified a new risk allele <i>HLA-DPB1*09∶01</i> (P = 1.36×10<sup>−6</sup>; OR = 1.97; 95% CI, 1.50–2.59) and a new protective allele <i>DPB1*02∶01</i> (P = 5.22×10<sup>−6</sup>; OR = 0.68; 95% CI, 0.58–0.81) to chronic HBV infection, in addition to the previously reported alleles. Moreover, <i>DPB1*02∶01</i> was also associated with a decreased risk of disease progression in chronic HBV patients among Asian populations (P = 1.55×10<sup>−7</sup>; OR = 0.50; 95% CI, 0.39–0.65). Trans-ethnic association analyses identified Asian-specific associations of <i>HLA-DP</i> alleles and haplotypes with HBV infection or disease progression. The present findings will serve as a base for future functional studies of HLA-DP molecules in order to understand the pathogenesis of HBV infection and the development of hepatocellular carcinoma.</p></div>