诱导型一氧化氮合酶及肿瘤坏死因子-α基因多态与矽肺易感性

Polymorphisms of Inducible Nitric Oxide Synthase Gene, Tumor Necrosis Factor-α Gene and Susceptibility to Silicosis

目的探讨诱导型一氧化氮合酶(iNOS)基因和肿瘤坏死因子-α(TNF-α)基因多态性与矿工矽肺易感性的关系.方法采用病例对照设计,以男性矽肺病人184例为病例组,111例无矽肺的男性接尘矿工为对照组.应用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)技术检测iNOS Ser608Leu和TNF-α-308位点的多态性.结果 iNOS Ser608Leu位点携带T等位基因(C/T或T/T)的个体患矽肺的危险性降低(OR=0.48,95%CI=0.29～0.80),且与矽肺期别相关(P＜0.01).在矽尘高暴露组中,T等位基因的保护作用明显(OR=0.43,95%CI=0.24～0.78).TNF-α-308基因多态与矽肺危险性之间无相关性(P＞0.05),但携带A等位基因(G/A或A/A基因型)的吸烟工人更易发生矽肺(OR=2.48,95%CI=1.16～5.32).结论iNOS基因16外显子C＞T突变可能是抵抗矽肺发生和发展的保护因素,TNF-α-308位点基因多态在矽肺发病的遗传易感因素中不起主要作用,但该多态性与吸烟有交互作用.

Purpose To explore the rdationship between polymorphisms of iNOS gene, TNF-α gene and genetic susceptibility of silicosis. Methods A case-control study was designed and conducted. The case group was 184 male patients with silicosis and the control group was 111 male silicosis-free miners exposed to silicon dust. polymerase chain reaction-restrained fragment length polymorphism technique （PCR-RFLP） was applied to detect the single nucleotide polymorphisms （SNPs） of iNOS Ser608Leu and TNF-α-308. Results There was a 0.48-fold （95%CI=0.29-0.80） decrease risk of silicosis for individuals with T allele（either the heterozygous C/T or the homozygous T/T）compared with individuals carrying genotypes of homozygous C/C, and iNOS Ser608Leu was associated with silicosis upgrading（P〈0.01）. The protection effect of the iNOS polymorphism was particularly detected in the high exposure group（OR=0.43,95% CI=0.24-0.78）. No association was observed between TNF-α-308 polymorphism and silicosis. TNF-α-308 polymorphism had synergistic effect with smoking, for smokers with A allele were more susceptible to silicosis（OR=2.48, 95% CI=1.16-5.32） than smokers without A allele. Conclusions The C/T mutation of iNOS exon 16 might contribute to be a preventive factor to silicosis. Though TNF-α-308 polymorphism was not a susceptible factor to silicosis, it had a synergistic effect with smoking.