人类NRAMP1基因单核苷酸多态与接尘工人肺结核易感性

目的 探讨人类自然抵抗相关巨噬细胞蛋白1（NRAMP1）基因多态性与接尘工人肺结核易感性的关系.方法 采用1：2病例对照设计,按年龄相差小于5岁,工种、吸烟、饮酒率、总粉尘接触量和矽肺患病同比例匹配,选择61例男性肺结核患者为病例组（矽肺50例、非矽肺11例）,122例男性无肺结核者为对照组（矽肺100例、非矽肺22例）.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NRAMP1 INT4和D543N位点的多态性.结果 NRAMP1 INT4多态位点野生纯合子（G/G）、杂合子（G/C）和突变纯合子（C/C）在病例组的分布频率分别为63.9%、34.4%、1.6%,与对照组比较,差异有统计学意义（P＜0.05）,NRAMP1 INT4 C等位基因携带者患肺结核的危险性升高（OR=2.73,95% CI：1.32～5.64）,D543N位点多态与接尘工人肺结核易感性之间无关联（P＞0.05）.结论 NRAMP1基因第4内含子G＞C单核苷酸可能是接尘工人肺结核的易感因素.

Relationship between single nucleotide polymorphisms of NRAMP1 gene and susceptibility to pulmonary tuberculosis in workers exposed to silica dusts

OBJECTIVE: To explore the relationship between polymorphisms of natural resistance-associated macrophage protein 1 (NRAMP1) gene and genetic susceptibility of pulmonary tuberculosis (PTB) in workers exposed to silica dusts. METHODS: A 1:2 case control study of 61 male workers with PTB (50 silicosis patients and 11 unsilicosis workers) as the case group and 122 male PTB-free workers (100 silicosis patients and 22 unsilicosis workers) as the control group was conducted with the frequency matched for age of +/- 5 years, the job, the silica exposure, and the condition of cigarette smoking and alcohol drinking. The polymerase chain reaction-restrained fragment length polymorphism technique (PCR-RFLP) was used to detect the single nucleotide polymorphisms (SNPs) of NRAMP1 INT4 and D543N. RESULTS: There was a 2.73 times (95% CI: 1.32 approximately 5.64) increased risk of silicosis for individuals with C allele of NRAMP1 INT4 compared with individuals carrying homozygote (G/G), while SNPs of NRAMP1 D543N was not associated with PTB (P > 0.05). CONCLUSION: The G > C mutation of intron 4 of NRAMP1 gene might be a susceptible factor of silica for the workers exposed to PTB.