Study On Associations Between Rantes Polymorphisms And HBV-Related Liver Disease Susceptibility

Objectives:To investigate the genotypic and allelic distribution of the regulated upon activation normal T cell expressed and secreted (RANTES) gene in Guangxi population; and to evaluate the associations between genetic polymorphisms of RANTES-403G/A (rs2107538) and-28C/G (rs2280788) and HBV-related chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC) susceptibility. These findings will provide new genetic indicators for effective prevention and treatment of HBV-related liver diseases.Methods:A total of 413 HBV infected patients, (including 101 CHB,83 LC and 229 HCC), and 229 healthy controls were recruited from Guangxi region. SNPs of RANTES gene (rs2107538 and rs2280788) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by DNA sequencing; Genotypic and allelic frequencies were calculated using direct counting method. Hardy-Weinberg equilibrium (HWE) among each group respectively was analyzed by a goodness-of-fit Chi-square (χ2) test. The distributions of genotypic and allelic frequencies between groups were compared using Chi-square (χ2) test or Fisher’s Exact Test when it is appropriate. Applying logistic regression with adjustment for confounding factors and calculating odds ratios (ORs) and 95% confidence intervals (95% CIs), we estimate the effects of RANTES polymorphisms on the risk of HBV-related liver diseases.. Haplotype analyses were conducted using SHEsis software.Results:1. The genotypic distributions of RANTES-403G/A(rs2107538) and-28C/G (rs2280788) among each group followed HWE (all P> 0.05), which indicated that samples were representative and comparable.2. Three genotypes of RANTES-403 (GG, GA, AA) and RANTES-28 (CC, CG, GG) were detected in Guangxi population. And their frequencies were similar to the Asians, but not to the Caucasians and the Blacks.3. A significant association between RANTES-28C/G (rs2280788) polymorphism and increased risk of HBV-related HCC was found among Guangxi Zhuang population:CG vs.CC, OR=3.044,95%CI,1.285-7.211; CG+GG vs.CC, OR=2.974,95%CI=1.284-6.892; G vs.C, OR=2.491, 95%CI=1.178-5.268. RANTES-403G/A (rs2107538) and-28C/G (rs2280788) polymorphisms were not associated with the risk of HBV-related CHB, LC and HCC among Guangxi Han population (all P> 0.05).4. The RANTES-403G/A (rs2107538) polymorphisms were significantly associated with decreased risk of CHB among women:GA vs. GG, OR=0.270, 95% CI= 0.073-0.999; GA+AA vs. GG, OR= 0.276,95% CI=0.081-0.940. RANTES-403G/A (rs2107538) and-28C/G (rs2280788) polymorphisms were not associated with risk of HBV-related CHB, LC and HCC among man (all P> 0.05).5. The synergic effects of RANTES-403G/A (rs2107538) and-28C/G (rs2280788) polymorphisms to age, tobacco, alcohol were not significantly associated with HBV-related CHB, LC and HCC (all P> 0.05).6. Four haplotypes including C28A403、C28G403、G28A403、G28G403 of RANTES-403G/A and-28C/G were detected. However, there were no significant associations between those haplotypes and risk of HBV-related CHB, LC and HCC (all P>0.05).Conclusions:The present study suggest that the RANTES-28CG and G allele may increase the risk of HBV-related HCC among Guangxi Zhuang population, whereas RANTES-403GA may be a protective factor for CHB among women.