| Objective Hepatitis C virus(HCV)infection is an important risk factor for Liver Cirrhosis(LC)and Hepatocellular Carcinoma(HCC).The interaction between virus and host plays an important role in the development of LC and HCC.Several single nucleotide polymorphisms(SNPs)associated with the susceptibility to HCV-related LC and HCC have been extensively studied in foreign populations,such as "MHC class I antibody-related sequence A,MICA,rs2596542,DEPDC5 rs1012068,PNPLA3,rs738409,vitamin D receptor,VDR,rs7975232 and EGF,rs4444903.The allele and genotype frequencies of SNPs were significantly different among races.Since no study was reported in china,we selected the five SNPs to test whether they were associated with the susceptibility to HCV-related Cirrhosis in Chinese Han population.Methods This study was divided into two parts.The first part retrieved the SNPs associated with HCV infection-related Cirrhosis and HCC susceptibility in the NCBI(National Center for Biotechnology Information)database,and 62 cases of cirrhotic patients(case group)and 79 patients with chronic hepatitis C(control group)were collected by case-control study.All patients were genotyped by matrix-assisted laser desorption / ionization time of flight mass spectrometry(MALDI-TOF MS).statistical analysis was used to confirm whether these SNPs were associated with the susceptibility to HCV-related Cirrhosis in Chinese Han population.In the second part of the experiment,we collected and genotyped the five single nucleotide genotypes in 46 patients with HCV-related HCC,and analyzed whether these SNPs were associated with the susceptibility to HCV-related HCC.Results In the first part of the experiment,the results :(1)The association between rs2596542 locus of MICA gene and susceptibility to LC was not found: The frequency of GG,GA and AA genotype in cirrhosis group was 46.77%?41.94% and 11.29% respectively,compared with hepatitis group(58.23%,34.18%,7.59%),the difference was not statistically significant.The distribution frequency of G allele in liver cirrhosis group was 67.74% compared with that in hepatitis group(75.32%),the difference was not statistically significant.The rs2596542 was not found to beassociated with the susceptibility to HCV-related Cirrhosis in a multivariate Logistic regression model of adjusted age,gender,and other factors.(2)The association between rs1012068 locus of DEPDC5 gene and susceptibility to LC was not found: The frequency of GG,GA and AA genotype in cirrhosis group was 54.84%?35.48% and 9.68% respectively,which was not statistically significant compared with hepatitis group(60.76%,36.71%,2.53%).The distribution frequency of T allele in liver cancer group was 72.58%,which was not statistically significant compared with hepatitis group(79.11%).The rs1012068 genotype was not found to be associated with the susceptibility to HCV-related Cirrhosis in a multivariate logistic regression model of adjusted age,gender,and other factors.(3)The association between rs738409 locus of PNPLA3 gene and susceptibility to LC was not found:The genotype frequencies of GG,GA and AA in the cirrhosis group were 37.10% ? 46.77% and 16.13% respectively,which was not statistically significant compared with hepatitis group(44.30%,43.04%,12.66%).The distribution frequency of C allele in hepatocellular carcinoma group was 60.48%,which which was not statistically significant compared with hepatitis group(65.82%).The rs738409 genotype was not found to be associated with the susceptibility to HCV-related Cirrhosis in a multivariate Logistic regression model with adjusted age and gender.(4)The association between rs7579232 locus of VDR gene and susceptibility to LC was not found:The frequency of GG,GA and AA genotype in liver cancer group was 58.06%?38.71% and 3.23% respectively,which was not statistically significant compared with hepatitis group(49.37%,45.57%,5.06%).The distribution frequency of C allele in hepatocellular cirrhosis group was 77.42%,which which was not statistically significant compared with hepatitis group(72.15%).The rs7975232 genotype was not found to be associated with the susceptibility to HCV-related Cirrhosis in a multivariate Logistic regression model of adjusted age,gender,and other factors.(5)The rs4444903 locus of EGF gene was associated with the susceptibility to LC: the frequencies of GG,AG and AA genotypes were 61.30%?31.25% and 6.45% in case group,respectively.Compared with hepatitis group(40.50%,51.90%,7.60%,the difference was not statistically significant.The frequency of allele G in cirrhosis group and hepatitisgroup group was 77.42% and 66.46% respectively,the difference was not statistically significant(P = 0.073).In multivariate logistic regression analysis,GG genotype was significantly associated with HCV-related Cirrhosis compared to the AA+AG genotype and allele G is the risk allele after an adjustment on age,gender,body mass index(BMI),duration of HCV infection and HCV RNA level(OR = 3.104;95%CI = 1.319-7.307;P = 0.010).In the second part,the results:(1)The rs4444903 was associated with the susceptibility to HCC: the frequencies of GG,GA and AA genotypes were 60.87%?32.61% and 6.52% in hcc group,respectively.Compared with hepatitis group(40.50%,51.90%,7.60%),there was not statistical significance(P = 0.083).The frequency of allele G in hcc group and hepatitis group group was 77.17% and 66.46%,respectively,there was not statistical significance(P=0.073).In multivariate logistic regression analysis,GG genotype was significantly associated with HCV-related HCC compared to the AA+AG genotype and allele G is the risk allele after an adjustment on age,gender,body mass index(BMI),duration of HCV infection and HCV RNA level(OR = 1.944,95% CI: 1.023-3.695,P = 0.042).(2)The association between rs2596542,rs1012068,rs738409 and rs7975232 and the susceptibility to HCV-related HCC was not found in this study population.Conclusion(1)EGF rs4444903 was associated with the susceptibility to HCV-related LC and HCC.(2)The associations between rs2596542,rs1012068,rs738409 and rs7975232 and the susceptibility to HCV-related LC and HCC were not found in this experiment. |
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