Association Of IL-21 And IL-18 Gene Polymorphisms With Hepatocellular Carcinoma Caused By The Hepatitis B Virus

Objectives To investigate the association of the rs2221903, rs907715 and rs1250872 single nucleotide polymorphisms( SNPs) within interleukin-21 gene and-137G/C、-607A/C within IL-18 gene with hepatocellular carcinoma caused by the hepatitis b virus, We study the distribution frequency of five SNPs in healthy controls, patients with chronic hepatitis B who had not been developed into liver cancer and patients with HBV-related HCC.Methods Studied subjects were divided into threre groups: patients with HBV-related HCC, patients with chronic hepatitis B virus infection,healthy controls. The polymerase chain reaction-ligase detection reaction(PCR-LDR) strategy was used to detect alleles and genotypes of IL-21 gene rs2221903, rs907715 and rs1250872 and IL-18 gene-137G/C and-607A/C. Statistical analysis was performed by SPSS version 19.0statistical software. Differences in quantitative traits were analyzed by t test.Differences in discrete variables were analyzed using χ2 analysis. Logistic regression analysis was used to analyze the association between differentdistribution of genotypes and the risk of HBV-related hepatocellular carcinoma.Results1. The differences of age and gender among patients with HBV-related HCC, patients with chronic hepatitis B virus infection and healthy controls were no statistical significance(P>0.05). The genotype frequencies of rs2221903, rs907715 and rs12508721 SNPs within IL-21 gene and-137G/C and-607A/C within IL-18 gene in each group were in agreement with the theoretical proportions of Hardy–Weinberg equilibrium(P>0.05).2. For IL-21 gene:(1) The genotype AG distribution frequency of the rs2221903 polymorphisms in chronic HBV infected group(29.6%) was higher than that in healthy control group(18.1%) and there was statistical significance(P=0.036). The AG genotype of the rs2221903 SNP was associated with increased risk of chronic HBV infection when compared with healthy controls(OR=1.898, 95%CI: 1.038-3.471).(2) The genotype TT distribution frequency of the rs12508721 polymorphisms in chronic HBV infected group(11.3%) was lower than that in healthy control group(22.0%) and there was statistical significance(P=0.026). The TT genotype of rs12508721 SNP was associated with lower risk of chronic HBV infection when compared with healthy controls(OR=0.451, 95%CI:0.221-0.920).(3) The genotype TT distribution frequency of thers12508721 polymorphisms in HBV-related HCC patients(12.0%) was lower than that in healthy control group(22.0%) and there was statistical significance(P=0.049). The TT genotype of rs12508721 SNP was associated with lower risk of chronic HBV infection when compared with healthy controls(OR=0.482, 95%CI=0.231-1.005).(4) No significant difference in the genotype and allele distrubutions of rs907715 SNP was observed in the HBV-related HCC group, chronic HBV infected group and the healthy control group when compared to each other.(5) The genotype and allele distributions of the three SNPs(rs2221903, rs907715 and rs12508721) showed no significant difference in the chronic HBV infected subgroups and HBV-related HCC group.3. For IL-18 gene:(1) There was statistical significance in the AA genotype and A allele distributions of-607A/C between the groups of HBV-related HCC(29.4%、54.6%)and healthy controls(18.1%、44.1%)(P<0.05). The AA genotype and A allele were associated with the higher risk of HBV-related HCC(OR=1.879, 95%CI : 1.020-3.464; OR=1.524,95%CI: 1.059-2.193).(2) There was statistical significance in the A allele distribution between the groups of choric HBV infection( 54.0%) and healthy controls(44.1%)(P<0.05). The A allele was associated with the increased risk of chronic HBV infection(R=1.487, 95%CI: 1.037-2.132).(3) The genotype and allele distributions of the two SNPs(-607A/C and-137G/C) showed no significant difference in the chronic HBV infectedsubgroups and HBV-related HCC group.Conclusions1. Our findings suggested that the rs12508721 polymorphisms within IL-21 gene and the-607A/C polymorphisms within IL-18 gene were associated with the susceptibility of HBV-related HCC. The risk of patients carrying TT genetype of rs12508721 developing into HBV-related HCC was significantly reduced. The risk of patients carrying AA genetype and A allele of-607A/C developing into HBV-related HCC was both significantly increased. 2. The rs2221903 polymorphisms and rs12508721 polymorphisms within IL-21 gene and the-607A/C polymorphisms within IL-18 gene were associated with the susceptibility of chronic HBV infection. The susceptibility of patients carrying AG genetype of rs2221903 developing into chronic HBV infection was significantly increased. The risk of patients carrying TT genetype of rs12508721 developing into chronic HBV infection was significantly reduced. The risk of patients carrying A allele of-607A/C developing into chronic HBV infection was significantly increased.