| Objective:Reactive oxygen species (ROS) play critical roles in DNA damage and cell death. The catalase (CAT) enzyme is an endogenous antioxidant enzyme, which involved in the repair of ROS. Therefore, we investigate the association between CAT gene rs1001179, rs769217, and rs7943316 polymorphisms and the risk of chronic hepatitis B (CHB), hepatitis B virus related liver cirrhosis (HBV-LC), and hepatocellular carcinoma (HBV-HCC) in Guangxi Chinese population.Methods:A total of 715 subjects were divided into four groups:111 CHB patients,90 HBV-LC patients,266 HBV-HCC patients, and 248 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect CAT gene rs 1001179, rs769217, and rs7943316 polymorphisms. DNA sequencing method was used to verify the genotype results. A binary logistic regression model was used to obtain the estimated odds ratios (ORs) and 95% confidence intervals (CIs) after adjusting for potential confounding variables such as gender, age, ethnicity, smoking and alcohol consumption, and body mass index.Results:1. The genotype distributions of rs 1001179 and rs7943316 were found to be in Hardy-Weinberg equilibrium in the control and case group, suggesting that data were from the same Mendelian population.2. There were three genotypes (GG, AG and AA) in rs1001179 site. Logistic regression analysis for the CAT rs 1001179 polymorphism revealed no differences in allele and genotype frequencies distribution between cases and controls. The CAT rs 1001179 polymorphisms were not associated with CHB, HBV-LC, and HBV-HCC risk in any analytic models.3. There were three genotypes (CC, CT and TT) in rs769217 site. Analysis for the CAT rs769217 polymorphism indicated that subjects carrying the rs769217 TT genotype had a moderately increased risk for CHB, HVC-LC, and HBV-HCC compare to CC genotype, with adjusted ORs of 2.11 (95% CI= 1.05-4.22; P=0.035),2.00 (95% CI=1.01-3.95;P=0.047), and 1.93 (95% CI =1.14-3.28; P=0.015), respectively. Moreover, subjects carrying the rs769217 CT genotype and at least one copy of the T allele (dominant model) were 1.78 times and 1.83 times more likely to develop HBV-HCC, respectively (OR=1.78, 95% CI=1.16-2.73, P=0.009 and OR=1.83,95% CI=1.23-2.71, P=0.003). Similarly, those individuals carrying the rs769217 T allele were at marginally increased risk of CHB, HBV-LC, and HBV-HCC when compared to carriers of the C allele, with adjusted ORs of 1.51 (95% CI=1.04-2.20; P=0.029),1.48 (95% CI=1.03-2.14; P=0.035), and 1.51 (95% CI=1.14-1.98; P=0.004), respectively.4. There were three genotypes (AA, AT and TT) in rs7943316 site. Logistic regression analysis for the CAT rs7943316 polymorphisms revealed that rs 1001179 polymorphisms were not associated with CHB, HBV-LC, and HBV-HCC risk in any analytic models.5. Subgroup analyses suggested that association between variants in CAT rs769217 and HBV-HCC risk was significantly strengthened among men, nonsmokers, nondrinkers, and among individuals younger than 50 years of age.6. There was no linkage disequilibrium among CAT rs 1001179, rs769217 and rs79433167. Furthermore, we found one high risk haplotype GTA for CHB (OR=1.449,95%CI=1.046-2.007, P=0.025), HBV-LC (OR=1.57,95%CI =1.11-2.23, P=0.011) and HBV-HCC (OR=1.49,95%CI=1.16-1.92, P= 0.002), and one protective haplotype GCA for HBV-LC risk (OR= 0.56,95%CI =0.38-0.82, P=0.003) and HBV-HCC risk (OR=0.67,95% CI=0.52-0.87, P =0.003).Conclusion:Our findings suggest that variants in CAT rs769217 were associated with increased risk of CHB, HBV-LC, and HBV-HCC in the Guangxi population. |
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