Interleukin-18基因启动子区单核苷酸多态性与肝细胞癌遗传易感性关系的研究

The correlation between single nucleotide polymorphism of interleukin-18 gene promoter and genetic susceptibility to hepatocellular carcinoma

目的探讨白细胞介素18(IL-18)基因启动子区-607C/A(rs1946518)和-137G/C(rs187238)单核苷酸多态性(SNP)与肝细胞癌(肝癌)遗传易感性的关系。方法应用序列特异性引物-聚合酶链反应(PCR-SSP)技术,检测228例肝癌患者和300例健康对照者IL-18基因启动子-607C/A(rs1946518)、-137G/C(rs187238)单核苷酸多态性位点基因型,分析肝癌患者和对照组基因型频率和等位基因频率分布。结果肝癌组SNP位点rs187238 G等位基因的频率明显高于对照组(OR=1.1891,95%CI=1.0106-1.5633,P=0.026)。携带rs187238 GG基因型的肝癌患者较多(OR=1.5168,95%CI=1.1490-1.8322,P=0.010)。分层分析发现,rs1946518位点上AA基因型与肝癌发病的关联在饮酒的肝癌患者中更加显著(P=0.024),而且rs187238位点上GC/CC基因型与肝癌发病的关联在出现肝癌复发的患者中更加显著(P=0.005)。结论 IL-18基因启动子区-137G/C(rs187238)GG基因型与肝癌遗传易感性有关联。而rs1946518位点AA基因型和rs187238位点GC/CC基因型分别与肝癌患者饮酒和肝癌复发有关联。

This study aimed to investigate the correlation between the single nucleotide polymorphism（SNP） of-607C/A（rs1946518） and-137G/C（rs187238） in the promoter region of the interleukin-18（IL-18） gene and genetic susceptibility to hepatocellular carcinoma（HCC）.The SNP at the position of IL-18 gene promoters-607C/A（rs1946518） and-137G/C（rs187238） were detected by sequence specific primer-polymerase chain reaction（SSP-PCR） in 228 patients with HCC and 300 matched controls.The genotype and allele frequencies were analyzed in both HCC patients group and control group.At rs187238,G allele frequency was significantly higher（OR=1.1891,95%CI=1.0106-1.5633,P=0.026） in HCC patients,and more HCC patients were carrying rs187238 GG genotype（OR=1.5168,95%CI=1.1490-1.8322,P=0.010）.Stratified analysis showed that rs1946518 AA genotype was significantly associated with high incidence of wine-drinking occurred in HCC patients（P=0.024）,and rs187238 GC/CC genotypes was significantly associated with high rate of tumor recurrence in HCC patients（P=0.005）.We come to a conclusion that the GG genotype of IL-18 gene promoter 137G/C（rs187238） is correlated with genetic susceptibility of HCC,while the AA genotype of rs1946518 and GC/CC genotype of rs187238 were respectively associated with high incidence of wine-drinking and tumor recurrence in HCC.