Association Between Genetic Polymorphism Of Interleukin-6 Gene Susceptibility To Liver Disease

ObjectivesTo study single nucleotide polymorphism(SNP)of rs1800795,rs1800796 and rs1800797 which located at the interleukin-6(IL-6)promoter region in GuangXi population.To analyze the association between SNP of rs1800795,rs1800796,rs1800797 and patients with chronic hepatitis B(CHB),liver cirrhosis(LC),hepatocellular carcinoma(HCC).To obtain the important haplotype or SNP which was associated with the susceptibility of CHB,LC,HCC and provide new genetic markers for the prevention of liver disease and new biological targets for the treatment of liver disease.MethodsDNA sequencing methods and Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)strategy were used to analyze the SNP of IL-6 in 192 healthy controls and patients with 185 CHB,92 LC and 192 HCC.SHEsis software was used to construct three SNP's haplotypes of IL-6.Serum IL-6 levels of four groups individual were detected by Roche Cobas · e601.The SNP genotype and allele frequency distribute were tested through x2 test.The logistic regression analysis was used to calculate odds ration(OR)and 95%confidence interval(95%CI)among different genotype and allele frequency.Analysis of variance was used to test serum IL-6 levels difference among four groups research individual and paired-samples T test was analyze IL-6 difference between before and after surgy in patients with HCC.All the statistical analysis was done by SPSS 13.0.Results1.The Hardy-Weinberg equilibrium which test rs1800795?rs1800796?rs1800797 located at IL-6 gene promoter were all consistent with Hardy-Weinberg equilibrium(HWE).The samples were representative and comparable(p>0.05).2.IL-6 SNPrs1088795 and rs1800796 were low mutation ratas in GuangXi area population.There were only GG?GC about rs1800795 and GG?GA about rs1800797.We did not detected CC of rs1800795 and AA of rs1800797.The genotypes and alleles of rs1800795 and rs1800797 were no statistically significant between healthy control and all cases(p>0.05).3.After logistic regressive analysis and regulating gender and age factors,we find that there should be some association between susceptibility of LC?HCC and IL-6 rs1800796.CG?GG genotype and G allele were associated with LC(the OR were 1.526,3.211,1.561 respectively).CG and GG genotype and G allele were also associated with HCC(the OR were 1.854,4.742,1.881 respectively).4.Both in male and female sub-group analysis,the rs1800795 and rs1800797 were all no associated among control and three cases.But for rs1800796,its GG genotype should be risk factors to CHB and HCC in male group.5.The frequency distribution of genotype and allele for rs1800795,rs1800796 and rs 1800797,which located in IL-6 promoter.region were similar with the results of south-east Asia area?yellow races.To Europe and North America area?white population were significant differences.6.The haplotype GGG of rs1800795,rs1800796,rs1800797 in the IL-6 promoter region was associated with CHB and HCC of GuangXi population,the OR were 1.67 and 1.83 respectively.7.both in the CHB and HCC case groups,the different serum IL-6 levels of patients who carried CC?CG and GG genotype were statistically significant.Compared with CC and CG genotype,the serum IL-6 level was higher than them.After HCC surgery,the serum IL-6 level would become lower than before surgery,it may result form that inflammatory response has become weaken?Conclusions1.The genotypes and alleles of rs1800795,rs1800796,rs1800797 which located at IL-6 gene promoter region in GuangXi population were similar with south-east Asia area?yellow race,and were different markedly with Europe and North America area?white race.2.The GG genotype and G allele of IL-6 rs1800796 should be risk factors for chronic hepatitis B and hepatocellular carcinoma among GuangXi population.