重庆汉族儿童IL-18基因启动子-137G/C多态性及蛋白表达与结核病易感性的关系

Association of IL-18 promoter polymorphisms with susceptibility to tuberculosis and its protein production in Chongqing Han children

目的:探讨重庆汉族儿童白介素-18(Interleukin18,IL-18)18基因启动子单核苷酸多态性(Single nucleotide polymorphism,SNP)与结核病易感性的关系及其对蛋白表达能力的影响。方法:序列特异性引物-聚合酶反应(Sequence specific primers-pdy merase chain reaotion,SSP-PCR)方法分析113名重庆汉族结核病患儿及167名健康儿童IL-18基因启动子(-607C/A和-137G/C)多态性;ELISA检测46例重庆汉族健康儿童PBMCs培养上清中IL-18的表达水平。结果:结核患儿组IL-18-137GG基因型的分布频率(81.4%)显著高于健康对照组(67.7%)(P=0.01),-137GC基因型的分布频率(16.8%)显著低于健康对照组(28.7%)(P=0.02);结核患儿组IL-18-137等位基因C分布频率(10.2%)明显低于健康对照(18.0%)(P=0.01);而结核患儿IL-18-607位各基因型及等位基因频率与健康对照比较无显著性差异。携带IL-18-137GG基因型儿童的PBMCs体外自发或经PMA+A23187活化后,表达IL-18蛋白的水平显著低于-137GC基因型者(P<0.01)。结论:IL-18-137位基因多态性可能与重庆儿童结核病易感性有关,等位基因G可能使IL-18蛋白低表达,是结核病的易感基因,而IL-18-607位基因多态性则可能与结核病易感性无关。

Objective：To investigate the association of IL-18 gene promoter SNPs with susceptibility to TB and its protein production in Chongqing Han children. Methods：Polymorphisms at -137 and -607 locus of IL-18 gene promoter in 113 TB child patients and 167 healthy controls were detected by SSP-PCR. The IL-18 productions in cultured supernatants of PBMCs from 46 healthy children were measured by ELISA. Results：The frequency of IL-18 -137GG genotype were significantly higher in TB patients（81.4%） than that in controls（67.7%）（P=-0.01）,while the frequencies of-137GC genotype（1.8% vs 3.6%） and -137C allele（ 10.2% vs 18.0%） were conversely lower（P〈0.05）,but the frequencies of alleles and genotypes at -607 were not statistically significant between the patients and the controls. Furthermore,-137GG genotype was significantly associated with lower IL-18 production compared with -137GC genotype when with or without PMA＋A23187 stimulation for 24h. Conclusions： The results showed that IL-18 gene promoter polymorphisms at position -137 confer susceptibility to TB in Chongqing Han children. Subjects carrying -137G allele at the promoter of IL-18 gene,which is associated with lowered IL-18 level,may be a high risk population of TB development.