Association Between Polymorphisms Of Interleukin-8 Gene And Susceptibility To Hepatitis B-Related Liver Disease

Objectives To investigate the distribution of interleukin-8 polymorphism in patients with hepatitis B-related hepatitis,liver cirrhosis or hepatocellular carcinoma in Guangxi; analyze the association of representative single nucleotide polymorphisms(SNP) with hepatitis B-related hepatitis , liver cirrhosis or hepatocellular carcinoma,providing new genetic markers for the prevention or treatment of hepatitis B-related liver disease .Methods 390 consecutive HBV infected-patients including 160 patients with chronic hepatitis B(CHB), 80 patients with HBV-induced liver cirrhosis(LC) and 150 patients with HBV-related hepatocellular carcinoma (HCC) admitted to our hospital for therapy and 150 healthy controls were considered .We identify the polymorphisms of the IL-8 gene at positions -25lA/T and +78lC/T,using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing; the Hardy-Weinberge quilibrium(HWE), genotype and allele frequencies were compared between case group and control group using SPSS 13.0 software. The independent risk and protective genotypes and alleles were screened out by logistic regression analyses.Odds ratio(OR)and 95% confidence intervals(CI) were calculated to assess the relative risk.The linkage disequilibrium(LD) test and haplotype of IL-8 polymorphism was performed using SHEsis software.Results1.The genotype distribution of IL-8 polymorphism was compatible with the Hardy-Weinberg equilibrium in case group and control group,the samples detected were representative and comparable.(P>0.05).2.There was no significant difference in the distribution of the genotype frequencies and allelic frequencies of the IL-8 gene +781C/T polymorphism and -251A/T polymorphism in different groups(P>0.05).3. After adjustment for age and sex by logistic regression analysis, compared with the TT genotype,the IL-8 gene -251A/T site AA genotype was associated with a significantly lower risk of liver cirrhosis(OR=0.135;95%CI,0.021-0.865;P=0.035).Using T allele as a reference, the risk of developing hepatic cirrhosis was decreased by 47.7% at the presence of A allele (95%CI,0.247-0.920;P=0.027).The polymorphisms of +781C/T site might be not associated with the risk in CHB, LC or HCC in Guangxi population.4. Both in the male and female population, no significant difference in the distribution of the genotype frequencies and allelic frequencies of the IL-8 gene +781C/T polymorphism and -251A/T polymorphism in different groups(P>0.05). And the two SNPs might be not associated with the risk in CHB, LC or HCC in Guangxi population.5.The distribution of the two SNPs in Guangxi population was not significantly different in European and Beijing population,but was significantly different in Nigerian and Japanese population.6.Linkage disequilibrium(LD) test and haplotype analysis indicated that: 1) there was a linkage disequilibrium between IL-8 gene -251A/T and +781C/T(D'=0.710,r2=0.356,P<0.001); 2) there were four haplotypes—A²⁵¹C⁷⁸¹, A²⁵¹T⁷⁸¹, T²⁵¹C⁷⁸¹ and T²⁵¹T⁷⁸¹; 3) none haplotypes significantly increased the risk of B-related liver disease.Conclusion IL-8 gene -251A/T AA genotype and A allele may play a protective role in HBV-induced liver cirrhosis in Guangxi population.