Genetic variants of interferon regulatory factor 5 associated with chronic hepatitis B infection

摘要

AIM To investigate possible effects of IRF5 polymorphisms in the 3' UTR region of the IFR5 locus on susceptibilityto hepatitis B virus(HBV) infection and progression of liver diseases among clinically classified Vietnamese patients.METHODS Four IFR5 SNPs(rs13242262 A/T, rs77416878 C/T, rs10488630 A/G, and rs2280714 T/C) were genotyped in clinically classified HBV patients [chronic hepatitis B(CHB). n = 99; liver cirrhosis(LC), n = 131; hepatocellular carcinoma(HCC), n = 149] and in 242 healthy controls by direct sequencing and Taq Man realtime PCR assays. RESULTS Comparing patients and controls, no significant association was observed for the four IFR5 variants. However, the alleles rs13242262 T and rs10488630 G contributed to an increased risk of liver cirrhosis(LC vs CHB: OR = 1.5, 95%CI: 1.1-2.3, adjusted P = 0.04; LC vs CHB: OR = 1.7, 95%CI: 1.1-2.6, adjusted P = 0.019). Haplotype IRF5*TCGT constructed from 4 SNPs was observed frequently in LC compared to CHB patients(OR = 2.1, 95%CI: 1.2-3.3, adjusted P = 0.008). Haplotype IRF5*TCAT occurred rather among CHB patients than in the other HBV patient groups(LC vs CHB: OR = 0.4, 95%CI: 0.2-0.8, adjusted P = 0.03; HCC vs CHB: OR = 0.3, 95%CI: 0.15-0.7, adjusted P = 0.003). The IRF5*TCAT haplotype was also associated with increased levels of ALT, AST and bilirubin. CONCLUSION Our study shows that IFR5 variants may contribute as a host factor in determining the pathogenesis in chronic HBV infections.