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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 investigate the relationship between IFN - γ gene +874 SNP and susceptibility to pulmonary tuberculosis as well as its effect on IFN-γ secretion. Methods The genotypes of IFN-γ gene +874 in 142 pulmonary tuberculosis patients and 166 healthy control subjects were genotyped by TaqMan probe genotyping and case-control study. The allele frequencies of two groups were compared. The levels of IFN-γ secreted by peripheral blood plasma and PBMC in different genotypes were determined, and the relationship between genotypes and IFN-γ secretion was clarified. Results The allele of T and A at +874 locus of IFN-γ gene was 88.0% and 12.0% respectively in tuberculosis group. The frequencies of A and T allele in control group were 81.0% , 19.0% respectively. The difference between the two groups was statistically significant (P <0.05, OR = 1.72, 95% CI 1.09 ~ 2.70). Tuberculosis patients with peripheral plasma levels of IFN-γ in different genotypes showed no significant difference (P> 0.05). After PBMC stimulation with TB lysate, the IFN-γ of the TT genotype was (754.8 ± 102.9) pg / mL, which was significantly higher than that of the AA genotype (648.9 ± 80.83) pg / mL, with significant difference (P <0.05). Conclusion The +874 polymorphism of IFN-γ gene is associated with the susceptibility to tuberculosis. The A allele is a susceptible gene of tuberculosis. The IFN-γ gene +874 polymorphism affects the expression of IFN-γ in the host, The immune process plays an important role.