Fas/FasL基因多态性与肝细胞癌易感性的关系

摘要

Objective To investigate the relationship between single nucleotide polymorphisms (SNPs) of apoptotic-related gene Fas/FasL and susceptibility to hepatocellular carcinoma (HCC).Methods Peripheral blood samples were collected from 126 patients with pathologically confirmed HCC in our hospital from January 2013 to December 2016.With the Sequenom MassARRAY system using matrix-assisted laser desorption Ionization (MALDI) time-of-flight mass spectrometry (TOFMS),genotyping of Fas polymorphic loci rs1571013,rs1800682 and rs1468063 and FasL polymorphic loci rs6700734 and rs763110 was carried out.The peripheral blood samples of 130 healthy subjects were used as control.Hardy-Weinberg equilibrium analysis was used to analyze the genetic balance of the above 5 SNPs loci.Comparison between HCC patients and healthy controls in terms of rs1571013,rs1800682,rs1468063,rs6700734 and rs763110 were made to calculate the odds ratio (OR) and its 95％ confidence interval (95％CI) to evaluate the relationship between SNPs and susceptibility to HCC.Results The distribution of 126 HCC patients and 130 healthy subjects regarding Fas polymorphism of rs1571013,rs1800682 and rs1468063 and FasL polymorphism of rs6700734 and rs763110 were in accordance with the Hardy-Weinberg equilibrium.There was no significant difference in the distribution of rs1468063,rs6700734 and rs763110 genotypes between the HCC group and the control group (P＞0.05),and had nothing to do with the susceptibility to HCC.As for the distribution of rs1571013,proportions of A/A genotype and A allele were higher in HCC group than those of the control group (P＜ 0.05).As compared to G/G genotype,A/A genotype increased the risk of HCC to 2.492 fold (P＜0.05),and the risk of HCC of A/ G and A/G+AA did not change (P＞0.05).Takng the G allele as the reference,risk of HCC for A increased to 1.549 folds (P＜ 0.05).As for the distribution of rs1800682,proportions of G/G genotype and G allele were higher in HCC group than those of the control group (P＜0.05).As compared to A/A genotype,G/G genotype increased the risk of HCC to 2.880 fold (P＜0.05) and the risk of HCC of A/G and A/G+G/G did not change (P＞0.05).Takng the A allele as the reference,risk of HCC for G increased to1.651 folds (P＜0.05).Conclusion Fas rs1571013 and rs1800682 are associated with HCC susceptibility and the risk of HCC carrying mutant alleles was increased,presenting certain value in screening susceptible individuals of HCC.%目的 探讨凋亡相关基因Fas及其配体FasL单核苷酸多态性(SNPs)与肝细胞癌(HCC)易感性的关系.方法 收集本院2013年1月至2016年12月经病理确诊的126例HCC患者的外周血标本,在Sequenom MassARRAY系统上利用基质辅助激光解吸电离飞行时间质谱法(MALDI-TOFMS)进行Fas多态性位点rs1571013、rs 1800682及rs 1468063和FasL多态性位点rs6700734、rs763110的基因分型,选取130例健康体检者的外周血作对比,采用Hardy-Weinberg平衡分析以上5个SNPs位点的遗传平衡情况,比较HCC患者与健康对照rs1571013、rs 1800682、rs1468063、rs6700734和rs763110基因型和等位基因的分布差异并计算比值比(0R)及其95％置信区间(95％CI)来评价以上SNPs与HCC易感性的关系.结果 126例HCC患者及130例健康体检者的Fas多态性位点rs1571013、rs 1800682及rs1468063和FasL多态性位点rs6700734及rs763110基因型的分布符合Hardy-Weinberg平衡.HCC组与对照组rs1468063、rs6700734和rs763110基因型分布的差异无统计学意义(P＞0.05),且与HCC易感性无关;rs1571013分布上,HCC组A/A基因型及等位基因A的比例均高于对照组(P＜0.05),其中以G/G基因型为参照,A/A基因型发生HCC的风险升高至2.492倍(P＜0.05),而A/G、A/G+A/A发生HCC的风险未改变(P＞0.05),以G等位基因为参照,A发HCC的风险升高至1.549倍(P＜0.05).rs 1800682分布上,HCC组G/G基因型及等位基因G的比例均高于对照组,差异有统计学意义(P＜0.05),以A/A基因型为参照,G/G基因型发生HCC的风险升高至2.880倍(P＜0.05),而A/G、A/G+G/G发生HCC的风险未改变(P＞0.05);以A等位基因为参照,G发生HCC的风险升高至1.651倍(P＜0.05).结论 Fas rs1571013、rs 1800682与HCC易感性有关,其中携带突变等位基因的HCC发生风险升高,在HCC易感人群筛查中有一定价值.