Association of genetic variation in B-cell activating factor with chronic hepatitis B virus infection

The outcome of hepatitis B virus (HBV) infection is considered to be related to the host immunogenetic susceptibility. B cell activating factor (BAFF) is involved in both B cell and T cell mediated immunity and its circulating levels were shown to be significantly elevated in HBV-related liver diseases. This study examined BAFF rs9514828 and rs12583006 polymorphisms in 386 patients with various liver diseases related to chronic HBV infection, 69 HBV infection resolvers, and 191 healthy controls. Both rs9514828 and rs12583006 polymorphisms and serum BAFF levels were determined in 232 patients with chronic HBV infection, and 61 healthy controls. The results showed that patients with chronic hepatitis had higher frequencies of rs9514828 genotype TT (19.75% vs. 11.86%, OR=2.397, 95% CI=1.121-5.125, P=0.023), genotypes CT+TT (74.69% vs. 63.55%, OR=1.478, 95% CI=1.050-2.080, P=0.045), and allele T (47.22% vs. 37.72%, OR=1.478, 95% CI=1.050-2.080, P=0.025) compared with patients with cirrhosis. Patients with chronic HBV infection and HBV infection resolvers had higher frequency of rs9514828 and rs12583006 haplotype TA compared with healthy controls (21.6% vs. 15.0%, OR=1.672, 95% CI=1.138-2.456, P=0.009 and 27.3% vs. 15.0%, OR=2.258, 95%CI=1.272-4.007, P=0.005, respectively). The rs9514828 and rs12583006 genotypes had no significant association with serum BAFF levels. These results suggest that the rs9514828 allele T may predispose to the liver inflammation in chronic HBV infection, and the rs9514828 and rs12583006 polymorphisms may combinatorially confer susceptibility to chronic HBV infection and resolution of the infection, possibly not through direct effect on serum BAFF levels.