Research On Correlation Between Polymorphism Of MiR196a-2 And PNPLA3 Genes With Chronic HBV Infection

Objective: To investigate the association between polymorphism of mi R196a-2 gene at rs11614913 and rs12304647 loci and polymorphism of PNPLA3 gene at rs738409 and rs139047 loci with different outcome of chronic HBV infection.Methods: A case-control study was carried out with Han nation people with chronic HBV infection in Qingdao area as the research objects,including a total of 54 patients with chronic hepatitis B(CHB),51 cases with HBV-related liver cirrhosis,53 cases with HBV-related hepatocellular carcinoma;and another 59 normal individuals were selected as the health control group.DNA was extracted from the whole blood,and direct sequencing was used to determine the genotypes of mi R196a-2 gene at rs11614913 and rs12304647 loci and genotypes of PNPLA3 gene at rs738409 and rs139047 loci.Unconditioned logistic regression was used for analysis,and odds ratio(OR)as well as 95% confidence interval(95% CI)were calculated.Results:(1)There were no statistically significant differences between health control group and case group in distribution of gender and age(P>0.05),they were comparable.(2)Allele frequencies at loci rs11614913,rs12304647,rs738409 and rs139047 of the health control group were in accordance with Hardy-Weinberg equilibrium(P>0.05),and the specimens are of demographic representation.(3)As for rs11614913 locus of mi R196a-2,the frequencies of genotype CC,TC,TT were 61.0%,28.8%,10.2% in health control group,72.2%,7.4%,20.4% in CHB group.There were statistically significant differences between CHB group and health control group in distribution of genotypes at rs11614913 locus of mi R196a-2(P<0.05);and the unconditioned logistic regression analysis found that,after correction of age and gender,genotype TC will significantly reduce the risk of chronic hepatitis B,compared with genotype CC(OR=0.22,95% CI=0.07-0.73).The frequencies of genotype CC,TC,TT were 66.7%,7.8%,25.5% in liver cirrhosis group.There were statistically significant differences between liver cirrhosis group and health control group in distribution of genotypes at rs11614913 locus of mi R196a-2(P < 0.05);and the unconditioned logistic regression analysis found that,after correction of age and gender,individuals carrying genotype TC and TC+TT had lower risk of liver cirrhosis,comparedwith genotype CC(OR=0.14,95% CI=0.03-0.61;OR=0.31,95% CI=0.10-0.95).The frequencies of genotype CC,TC,TT were 60.4%,5.7%,34.0% in hepatocellular carcinoma group.There were statistically significant differences between hepatocellular carcinoma group and health control group in distribution of genotypes at rs11614913 locus of mi R196a-2;and the unconditioned logistic regression analysis found that,after correction of age and gender,allele T would significantly increase the risk of hepatocellular carcinoma,compared with allele C(OR=1.79,95% CI=1.004-3.18);but the incidence of hepatocellular carcinoma was reduced in individuals carrying genotype TC,compared with genotype CC(OR=0.02,95% CI=0.001-0.25,P=0.003).(4)As for rs12304647 locus of mi R196a-2,the frequencies of genotype AA,AC,CC were 67.8%,27.1%,5.1% in health control group,57.4%,31.5%,11.1% in CHB group,62.7%,35.3%,2.0% in liver cirrhosis group,79.2%,17.0%,3.8% in hepatocellular carcinoma group.There were no statistically significant differences among CHB group,liver cirrhosis group,hepatocellular carcinoma group and health control group in distribution of genotypes at rs12304647 locus of mi R196a-2(P>0.05).(6)As for rs738409 locus of PNPLA3,the frequencies of genotype CC,GC,GG were27.1%,50.8%,22.0% in health control group,27.8%,38.9%,33.4% in CHB group.There were no statistically significant differences between CHB group and health control group in distribution of genotypes at rs738409 locus of PNPLA3(P > 0.05).The frequencies of genotype CC,GC,GG were 33.3%,15.7%,51.0% in liver cirrhosis group.There were statistically significant differences between liver cirrhosis group and healthy control group in distribution of genotypes at rs738409 locus of PNPLA3.The unconditioned logistic regression analysis found that,after correction of age and gender,individuals carrying genotype GC and GC+CC had lower risk of liver cirrhosis,compared with genotype GG(OR=0.03,95% CI=0.01-0.26;OR=0.28,95% CI=0.09-0.87).The frequencies of genotype CC,GC,GG were 18.9%,50.9%,69.8% in hepatocellular carcinoma group.There were statistically significant differences between hepatocellular carcinoma group and healthy control group in distribution of genotypes at rs738409 locus of PNPLA3.The unconditioned logistic regression analysis found that,after correction of age and gender,individuals carrying genotype GC had lower risk of hepatocellular carcinoma,compared with genotype GG(OR=0.10,95%CI=0.02-0.58).(7)As for rs139047 locus of PNPLA3,the frequencies of genotype AA,GA,GG were 25.4%,52.5%,22.0% in health control group,24.1%,55.6%,20.4% in CHB group,25.5%,45.1%,29.4% in liver cirrhosis group,24.5%,54.7%,20.8%in hepatocellular carcinoma group.There were no statistically significant differences among CHB group,liver cirrhosis group,hepatocellular carcinoma group and health control group in distribution of genotypes at rs139047 locus of PNPLA3(P>0.05).Conclusions:(1)Polymorphism of mi R196a-2 gene at rs11614913 locus may be associated with the occurrence of chronic hepatitis B in Han nationality in Qingdao,and genotype TC can significantly reduce the risk of chronic hepatitis B.(2)Polymorphism of mi R196a-2gene at rs11614913 locus may be associated with the occurrence of liver cirrhosis in Han nationality in Qingdao,and genotype TC and TC+TT can significantly reduce the risk of liver cirrhosis.(3)Polymorphism of mi R196a-2 gene at rs11614913 locus may be associated with the occurrence of hepatocellular carcinoma in Han nationality in Qingdao,and allele T can increase the risk of hepatocellular carcinoma,while genotype TC can reduce the risk of hepatocellular carcinoma.(4)Polymorphisms of PNPLA3 gene at loci rs139047 and polymorphism of mi R196a-2 gene at locus rs12304647 may be not associated with the occurrence of chronic hepatitis B,liver cirrhosis and hepatocellular carcinoma in Han nationality in Qingdao.(5)Polymorphisms of PNPLA3 gene at loci rs738409 may be not associated with the occurrence of chronic hepatitis B in Han nationality in Qingdao.Polymorphism of PNPLA3 gene at rs738409 is associated with the occurrence of liver cirrhosis,among which,genotypes GC and GC+CC can significantly reduce the risk of liver cirrhosis.And Polymorphism at rs738409 is associated with the occurrence of hepatocellular carcinoma,where genotype GC can significantly reduce the risk of hepatocellular carcinoma.