细胞毒性T淋巴细胞相关抗原4基因多态性与肝癌的易感性研究

Association of CTLA4 polymorphysims with susceptibility to hepatocellular carcinoma

摘要:

目的  本研究旨在探讨细胞毒性T淋巴细胞相关抗原4（CTLA4）外显子49位点、启动子1661位点及1722位点单核苷酸多态性（SNP）与青岛地区人群乙肝肝癌的易感性。方法  采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测来自青岛地区人群肝癌患者98例、非肝癌乙肝病毒感染组185例、健康对照组205例CTLA4基因型分布。结果  ①以健康人群为对照组CTLA4外显子49位点及启动子1661位点基因型频率分布差异有统计学意义（P <0.05），启动子1722位点基因型分布频率差异无统计学意义（P >0.05），CTLA4+49位点AG、GG 基因型携带者、CTLA4-1661位点AG+GG基因型携带者肝癌发病风险明显增高（■值分别为2.48、5.22及2.51）。②以非肝癌乙肝感染者为对照组，49位点AG、GG基因型、1661位点AG+GG基因型显著增加肝癌的发生风险（■值分别为2.48、4.60和2.13）。③以所有非肝癌者对照，49位点AG、GG基因型、1661位点AG+GG基因型显著增加肝癌的发生风险（■值分别为2.48、4.91及2.32）。结论  CTLA4外显子49位点、启动子1661位点基因多态性与肝癌易感性相关。

Abstract:

Objective To explore the correlation between several single-nucleotide polymorphism (SNP) loci on CTLA4 gene and the susceptibility to hepatocellular carcinoma in Qingdao area. Methods This case-control study included 98 patients diagnosed as hepatocellular carcinoma, 185 case with chronic hepatitis B and 205 healthy people. PCR-RFLP was used to study the genotype distribution of CTLA4 gene. Results The genotype frequency of CTLA4 +49 and -1661 loci showed significant difference between the hepatocellular carcinoma patients and the healthy people (P < 0.05). The frequency of distribution of CTLA4 -1722 locus had no significant difference between the hepatocellular carcinoma patients and the healthy people (P > 0.05). The additive odds ratio (■) of genotypes AG and GG in CTLA4 +49 locus and genotype AG+GG in CTLA4 -1661 locus for the risk of hepatocellular carcinoma was 2.48, 5.22 and 2.51 respectively. The frequency of genotypes AG and GG in CTLA4 +49 locus and genotype AG+GG in CTLA4 -1661 locus was higher in the hepatocellular carcinoma patients than in the chronic hepatitis B patients (■ = 2.48, 4.60 and 2.13 respectively). The frequency of genotypes AG and GG in CTLA4 +49 locus and genotype AG+GG in CTLA4 -1661 locus was higher in the hepatocellular carcinoma patients than in the non-HCC people (■ = 2.48, 4.91 and 2.32 respectively). Conclusions The single-nucleotide polymorphisms on CTLA4 +49 CTLA4 -1661 loci may play a landmark role in susceptibility to hepatocellular carcinoma.