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. 2014 Jun 18;9(6):e99724.
doi: 10.1371/journal.pone.0099724. eCollection 2014.

A genome-wide association study on chronic HBV infection and its clinical progression in male Han-Taiwanese

Su-Wei Chang  1 , Cathy Shen-Jang Fann  2 , Wen-Hui Su  3 , Yu Chen Wang  4 , Chia Chan Weng  4 , Chia-Jung Yu  5 , Chia-Lin Hsu  2 , Ai-Ru Hsieh  6 , Rong-Nan Chien  4 , Chia-Ming Chu  4 , Dar-In Tai  4
Affiliations

A genome-wide association study on chronic HBV infection and its clinical progression in male Han-Taiwanese

Su-Wei Chang et al. PLoS One. .

Abstract

It is common to observe the clustering of chronic hepatitis B surface antigen (HBsAg) carriers in families. Intra-familial transmission of hepatitis B virus (HBV) could be the reason for the familial clustering of HBsAg carriers. Additionally, genetic and gender factors have been reported to be involved. We conducted a three-stage genome-wide association study to identify genetic factors associated with chronic HBV susceptibility. A total of 1,065 male controls and 1,623 male HBsAg carriers were included. The whole-genome genotyping was done on Illumina HumanHap550 beadchips in 304 healthy controls and HumanHap610 beadchips in 321 cases. We found that rs9277535 (HLA-DPB1, P = 4.87×10(-14)), rs9276370 (HLA-DQA2, P = 1.9×10(-12)), rs7756516 and rs7453920 (HLA-DQB2, P = 1.48×10(-11) and P = 6.66×10(-15) respectively) were significantly associated with persistent HBV infection. A novel SNP rs9366816 near HLA-DPA3 also showed significant association (P = 2.58×10(-10)). The "T-T-G-G-T" haplotype of the five SNPs further signified their association with the disease (P = 1.48×10(-12); OR = 1.49). The "T-T" haplotype composed of rs7756516 and rs9276370 was more prevalent in severe disease subgroups and associated with non-sustained therapeutic response (P = 0.0262). The "G-C" haplotype was associated with sustained therapeutic response (P = 0.0132; OR = 2.49). We confirmed that HLA-DPB1, HLA-DQA2 and HLA-DQB2 loci were associated with persistent HBV infection in male Taiwan Han-Chinese. In addition, the HLA-DQA2 and -DQB2 complex was associated with clinical progression and therapeutic response.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. GWAS results.
Multi-stage signals of association with HBV infection in the HLA region.
Figure 2
Figure 2. LD patterns of the 5 SNPs.
LD patterns based on the D’ (left side) and r2 (right side) measures of the five associated SNPs for 625 individuals in the GWAS scan. The LD block built up by the rs9276370, rs7756516 and rs7453920 suggest that they were significantly associated with each other. The rs9366816 and rs9277535 SNPs were independent from each other and from the other three SNPs.
See this image and copyright information in PMC

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