, 2009). However, there have been no reports of HLA-DP genes to be associated with disease progression from CHB to liver cirrhosis (LC) or HBV-related hepatocellular carcinoma (HCC). PATIENTS/METHODS: We conducted HLA-DP genotyping using a total of 4,830 samples (including Japanese (n=2,954), Korean (n=586), Hong Kong (n=661) and Thai (n=629)) for HBV patients (including CHB,
LC and HCC), healthy controls and resolved individuals (HBsAg-nega-tive and anti-HBc-positive), based on PCR-SSO system according to manufacturer’s protocol. The Fisher’s exact test in a two-by-two cross table was applied to acquire exact P values. We used the DerSimonian-Laird method for a meta-analy-sis in four populations. The phase of each individual (i.e., a combination find more of two DPA1-DPB1 haplotypes) was estimated using PHASE software, assuming samples are selected randomly
PLX4032 clinical trial from a general population. RESULTS: A total of successfully genotyped 4,558 samples revealed one high-risk haplotype (HLA-DPA1*02:01-DPB1*09:01) and one protective haplotype (HLA-DPA1*01:03-DPB1*04:01) to be associated with CHB infection over the previously reported HLA-DP haplotypes in Asian populations (P= 3.38×10-6; OR=1.95; 95 %CI, 1.46-2.64 for HLA-DPA1*02:01-DPB1*09:01; P= 1.17×10-5; OR=0.32; 95 %CI, 0.18-0.56 for HLA-DPA1*01:03-DPB1*04:01). Moreover, a significant association of
DPB1*02:01 with protection not only against HBV infection but against disease progression from CHB to HCC, was identified in Asian populations (P= 1.55×10-7; OR=0.50; 95 %CI, 0.39-0.65). CONCLUSIONS: Trans-ethnic association study of HLA-DP in Asian populations revealed that specific HLA-DPB1 alleles (i.e. DPB1*02:01, *04:01, and *04:02) worked to be protective against HBV infection, and different alleles (i.e. DPB1*05:01, *09:01) worked to be susceptible Bay 11-7085 to HBV infection. To determine all the associated DPB1 alleles for HBV infection would enable HBV infected individuals to divide into two groups who need treatment or not. Moreover, DPB1*02:01 allele was associated with disease progression as well as CHB infection in Asian populations. DPB1 alleles would be key host factors to recognize HBV derived antigen peptides, which will lead the following functional studies of HLA-DP molecules in the future.