FAS和FASL基因多态性与矽肺易感性的关系

Polymorphisms of FAS and FASL genes and susceptibility of silicosis

目的探讨FAS和FASL基因多态性与矿工矽肺遗传易感性的关系。方法采用病例对照设计，以183例男性矽肺患者为病例组，111例无矽肺的男性接尘矿工为对照组，调查研究对象的一般情况及职业史，收集现场粉尘浓度资料，估算工人既往累积总粉尘接触量；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FAS-1377、FAS-670及FASL-844位点的多态性，分析多态性与矽肺患病及矽肺期别的关系，基因间以及基因与环境因素间的交互作用以及单倍型。结果FAS-1377、FAS-670及FASL-844各位点基因型在病例组和对照组间的分布差异均无统计学意义（P〉0．05）：不同期别矽肺患者中FAS-1377、FAS-670及FASL-844位点多态分布差异无统计学意义（P〉0．05）；病例组中FAS-1377G／-670G单倍型分布频率为9．6％，明显高于对照组（3．6％），差异有统计学意义（P〈0．05）；各基因多态间、基因多态与累积总粉尘接触量以及基因多态与吸烟状况之间的交互作用分析结果均无统计学意义（P〉0．05）。结论FAS-1377、FAS-670及FASL-844多态性在矽肺发病的遗传易感性中不起主要作用。单倍型FAS-1377G／-670G可能是矽肺发生的易感性标记。

Objective To explore the relationship between polymorphisms of FAS and FASL genes and genetic susceptibility of silicosis. Methods A case-control study was conducted. The case group was 183 male patients with silicosis and the control group was 111 male silica-exposed but without silicosis miners. Data on total dust concentrations was collected to estimate cumulative total dust exposure（CTE ） of each subject and each person＇s characteristics and work history were obtained from questionnaire. Polymerase chain reaction restrained fragment length polymorphism technique （PCR-RFLP） was applied to detect the single nucleotide polymorphisms （SNPs） of FAS-1377, FAS-670 and FASL-844. Associations between polymorphisms and risk of silicosis and stages, interactions between polymorphisms, between polymorphisms and CTE and smoking and haplotypes were analyzed. Results There were no differences in the FAS-1377,FAS-670 and FASL-844 genotypes between the case group and the control group （P〉0.05）. No association was observed between FAS-1377, FAS-670 and FASL-844 polymorphisms and silicosis and stages（P〉0.05）. The frequencies of FAS-1377G/-670G haplotype in the cases （9.6%） were higher than those in the controls （3.6%）（P〈0.05）. No interactions between the polymorphisms of different genes, the gene polymorphism and the total accumulative total dust, the gene polymorphism and smoking were observed （P〉0.05）. Conclusion FAS-1377, FAS-670 and FASL-844 polymorphisms are not susceptible factors of silicosis. The FAS-1377G/-670G haplotype might be a susceptibility marker of silicosis.