肿瘤坏死因子基因多态性与矽肺遗传易感性的研究

On the Association of Tumor Necrosis Factor-α Gene Polymorphisms with the Susceptibility to Silicosis

目的探讨肿瘤坏死因子α基因(tumornecrosisfactor-α,TNF-α)启动子区-308和-238位点G→A的碱基突变与中国西南地区汉族人群矽肺遗传易感性的相关性。方法分别选择在职的75例矽肺患者和137名矽尘接触者,140例高龄矽肺患者和135名高龄正常人为研究对象。采集外周静脉血,应用聚合酶链反应-限制性片段长度多态性分析和测序检测其TNF-α基因多态位点的变化。结果75例在职矽肺组中TNF-α-308A、-238A的分布频率显著高于矽尘接触组(P<0.01),其中期矽肺患者-308A的分布频率与矽尘接触组差异无统计学意义(P>0.01),而期、期矽肺患者-308A、-238A的分布频率均远高于矽尘接触组(P<0.01)。调整混杂因素后,Logistic回归分析发现,矽肺组及各亚组和正常矽尘接触组-308A、-238A的分布频率差异均有统计学意义(P<0.01)。而140例高龄矽肺患者TNF-α-308A的分布频率远低于正常对照组(P<0.001)。结论TNF-α-308及-238位点基因G→A的碱基突变与中国西南地区汉族人矽肺的发生及其严重程度有关,TNF2可能影响矽肺患者的转归和存活。

Objective To find out whether -308 and -238 locus （G→A） mutation within the tumor necrosis factor-α gene （TNF-α） promoter region are associated with susceptibility to silicosis in the Han population of southwest China. Methods Governed by the principles of voluntatiness and cooperation, 75 patients with silicosis and 137 control with silica-exposure but without silicosis were recruited, and additionally, 140 elderly patients with silicosis and 135 healthy elderly （retired） controls were recruited in this case-control study. 5 ml peripheral vein blood was drawn from each subject. By means of polymerase chain reaction-restriction fragment length polymorphisms （PCR-RFLP） and sequencing techniques, TNF-α gene polymorphisms of all subjects were analyzed. Results The frequencies of TNF-α -308A and -238A in the 75 patients with silicosis were higher than those in the 137 controls （P〈0. 01）. After being adjusted for confounding factors, the -308A and the -238A were still associated with the presence of silicosis（P〈0. 01）. But the frequency of TNF-α -308A in the 140 elderly patients was significantly lower than that in the controls （P〈0. 001）. Conclusions TNF-α gene -308 and -238 locus（G→A） mutation might be related to the occurrence of silicosis and the severity of pulmonary fibrosis in silicosis among the Han population of southwest China, and TNF2 （-308A） allele might increase the risk of the disease.