Association of Cytokine and Cytokine Receptor Gene Polymorphisms with the Risk of Chronic Hepatitis B

Abstract

Hepatitis B (HBV) infection is a major cause of chronic liver diseases, and the polymorphisms of cytokine genes may affect the progression of HBV-related hepatitis. The aim of this study was to examine the association of cytokine polymorphisms with the susceptibility to HBV-related chronicity. Specifically, a LIFECODES Cytokine SNP Typing kit was used to investigate 22 cytokine single nucleotide polymorphisms (SNPs) from 14 cytokine and cytokine receptor genes with the aim of analyzing the role of Th1 and Th2 genotype combination. This population-based case-control association study included 131 chronic HBV patients and a control group of 142 healthy donors. When the combination of Th1 and Th2 genotypes was analyzed for the genetic risk factor for chronic hepatitis B, we did not observe any significant association. A non-significant association betweenTh1 and Th2 and this risk factor could have resulted from the limitation of our small sample size. When the results from each genotype were separately analyzed, the frequencies of the heterozygous CA (-592) and CT (-819) genotype of IL-10 gene-promoter polymorphisms were significantly higher in chronic HBV patients than that in healthy controls (OR=1.76, 9%CI =1.03-3.01, p =0.028; OR=1.79, 95%CI =1.04-3.06, p =0.024, respectively). Interestingly, the TCC (-1098/-590/-33) haplotype frequency of IL-4 showed a positive association with chronic hepatitis B as a protective haplotype (OR =0.53, 95%CI =0.32-0.85, p =0.005). These preliminary results suggest that polymorphisms in some cytokine genes, particularly the Th2 cytokine, influence persistence of HBV infection.