Association Between IL-16 Genetic Variation, Hepatic Fibrosis And Risk Of Liver Diseases

Objective:To study polymorphisms of rs 11556218, rs4072111 and rs4778889 about IL-16 gene, we research the correlation between polymorphisms of IL-16 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. And dynamic analysis hyaluronic acid (HA), laminin (LN), collagen type IV (CIV), N-terminal procollagen III propeptide (PⅢ).To get the significant SNPs, haplotypes and serum markers that were correlation with HBV related liver diseases, obtaining novel genic and serum markers for the precaution and diagnosis of liver diseases and new target for the treatment of liver diseases.Methods:A total of 592 subjects were divided into four groups:129 CHB patients,129 HBV-LC patients,166 HBV-HCC patients, and 168 healthy controls. The PCR-RFLP strategy was used to detect IL-16 rs11556218T/G, rs4072111C/T and rs4778889T/C polymorphisms. DNA sequencing method was used to verify the genotype results. The estimated odds ratios (ORs) and 95% confidence intervals (CIs) using a binary logistic regression model was used to obtain after adjusting for potential confounding variables such as age, gender, ethnicity, smoking and alcohol consumption, and body mass index; Mann-Whitney U method is used to analysis association between serum markers of hepatic fibrosis and normal control group, CHB, hepatitis B virus related liver cirrhosis (HBV-LC) and hepatocellular carcinoma (HBV-HCC)Results:1. The genotype distributions of rs11556218T/G, rs4072111C/T and rs4778889T/C 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 (TT, TG and GG) in rs11556218T/G site. Logistic regression analysis for the IL-16 rs11556218T/G polymorphism revealed carrying the rs 11556218 G allele had a moderately increased risk for CHB compare to T allele(OR=1.51,95% CI=1.06-2.15, P= 0.021). However, G allele were not associated with HBV-LC and HBV-HCC risk, and no differences in genotype frequencies distribution between cases and controls.3. There were three genotypes (CC,CT and TT) in rs4072111C/T site. Logistic regression analysis for the IL-16 rs4072111C/T polymorphisms revealed that rs 1001179 polymorphisms were not associated with CHB, HBV-LC, and HBV-HCC risk in any analytic models.4.There were three genotypes (TT, TC and CC) in rs4778889T/C site. Analysis for the IL-16 rs4778889 polymorphism indicated that subjects carrying the rs4778889 TC genotype had a moderately decreased risk for HBV-HCC compare to CC genotype, with adjusted:OR= 0.56,95% CI=0.32-0.96, P= 0.036.However, TC genotype were not associated with CHB and HBV-LC risk. CC genotype and TC+CC genotype were not associated with CHB, HBV-LC, and HBV-HCC risk.5. Subgroup analyses suggested TG and TG+GG genotypes in rs 11556218 site increased risk of HBV-HCC for women; CT and CT+TT genotypes in IL-16 rs4072111 decreased risk of HBV-HCC among men, smokers, and among individuals younger than 50 years of age; TC and TC+TT genotypes in IL-16 rs4778889 decreased risk of HBV-HCC between men and among individuals younger than 50 years of age.6. We found one protective haplotype TCT for CHB risk (OR= 0.56, 95%CI= 0.38-0.82, P= 0.003), the other protective haplotype GTT for HBV-LC risk (OR= 0.38,95%CI= 0.16-0.90, P= 0.023. One high risk haplotype GCT for CHB (OR= 8.59,95%CI= 3.56-20.75, P= 0.001) and HBV-HCC (OR= 2.59,95%CI= 0.99-6.75, P= 0.044)7.CIV、HA and LN in HBV-LC were higher than the other groups, the second was HBV-HCC.PIIINP of CHB was higher than other groups, the HBV-HCC was higher than HBV-LC.Conclusion:1.The rs4778889 TC genotype had a moderately decreased risk for HBV-HCC, but the rs 11556218 G allele had a moderately increased risk for CHB compare to T allele; TG and TG+GG genotypes in rs 11556218 site increased risk of HBV-HCC for women; CT and CT+TT genotypes in IL-16 rs4072111 decreased risk of HBV-HCC among men, smokers, and among individuals younger than 50 years of age; TC and TC+TT genotypes in IL-16 rs4778889 decreased risk of HBV-HCC between men and among individuals younger than 50 years of age.2.One protective haplotype TCT for CHB risk, the other protective haplotype GTT for HBV-LC risk; One high risk haplotype GCT for CHB and HBV-HCC.3. CIV、HA、LN and PIIINP in CHB、HBV-LC and HBV-HCC were higher than the healthy controls.