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

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(O■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(O■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(O■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。

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（OR）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（OR= 2.48,4.60 and 2.13respectively）.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（OR= 2.48,4.91 and2.32 respectively）.Conclusions The single-nucleotide polymorphisms on CTLA4 ＋49 CTLA4-1661 loci may play a landmark role in susceptibility to hepatocellular carcinoma.