INF-γ基因+874位点SNP对肺结核易感性及蛋白分泌的影响

Effect of IFN-γ gene +874 single nucleotide polymorphism on susceptibility to tuberculosis and protein secretion

目的探讨干扰素-γ（IFN-γ）基因＋874位点单核苷酸多态性（SNP）与肺结核易感性的关系,以及对IFN-γ分泌水平的影响。方法应用TaqMan探针基因分型技术,采用病例-对照研究方法,对142例肺结核患者和166例健康对照人群IFN-γ基因＋874位点进行分型,比较两组人群等位基因频率差异,并测定不同基因型人群外周血浆以及PBMC分泌IFN-γ水平的差异,明确基因型与IFN-γ分泌水平的关系。结果 IFN-γ基因＋874位点具有T和A两种等位基因,其中结核组A、T等位基因频率分别为88.0%、12.0%,对照组A、T等位基因频率分别为81.0%、19.0%,两组差异具有统计学意义（P〈0.05,OR=1.72,95%CI 1.09~2.70）。结核患者外周血浆IFN-γ分泌水平在不同基因型之间差异无统计学意义（P〉0.05）。PBMC经过结核菌裂解物刺激后,TT基因型细胞上清IFN-γ为（754.8±102.9）pg/mL,显著高于AA基因型（648.9±80.83）pg/mL,差异有统计学意义（P〈0.05）。结论 IFN-γ基因＋874多态性位点与结核病易感性相关,A等位基因是肺结核易感基因;IFN-γ基因＋874多态性影响宿主IFN-γ表达水平,在调节肺结核保护性免疫过程中起重要作用。

Objective To explore the association between IFN-γ gene ＋874 single nucleotide polymorphisms（SNP）and susceptibility to pulmonary tuberculosis,and its influence on protein secretion. Methods A case- control study was conducted for determinating the genotype of IFN-γ gene ＋874 SNP in pulmonary tuberculosis（n=142）and healthy control group（n=166）with TaqMan assay. Quantification of IFN-γ levels in plasma or PBMC in patients with various genotypes was performed using ELISA. Results IFN-γ gene ＋874 SNP involved T and A allele,T and A allele frequency were 88.0%,12.0% in TB groups,and were 81.0%, 19.0% in healthy control group,showing significant difference between two groups（P0.05,OR=1.72,95%CI 1.09~2.70）. No significant difference was observed in IFN-γ plasma level among various genotypes（P0.05）,however,after Mtb lysate stimulation,PBMC with TT genotype had higher IFN-γ level than that with AA genotype（754.8±102.9 Vs 648.9±80.83pg/mL,P0.05）. Conclusion IFN-γ gene ＋874 SNP was associated with susceptibility to pulmonary tuberculosis,A allele was the susceptible allele for pulmonary tuberculosis. ＋874 SNP could influence the secretion of IFN-γ and played an important role in protective immune response against TB.