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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 investigate the relationship between the base mutation of G → A at -308 and -238 in the promoter region of tumor necrosis factor α (TNF-α) gene and the genetic susceptibility to silicosis in Han Chinese population in Southwest China. Methods Seventy five silicosis patients, 137 silicosis contacts, 140 elderly silicosis patients and 135 elderly normal subjects were enrolled in the study. Peripheral venous blood was collected and the changes of TNF-α gene polymorphism were detected by polymerase chain reaction-restriction fragment length polymorphism analysis and sequencing. Results The distribution frequency of TNF-α-308A and -238A in 75 cases of active silicosis patients was significantly higher than that of the silica dust exposure group (P <0.01). There was no significant difference in the distribution frequency of -308A between silicosis patients and silicosis exposure group (P> 0.01). However, the distribution frequency of -308A and -238A in patients with silicosis was significantly higher than that in silicosis exposure group (P <0.01). Logistic regression analysis showed that the distribution frequencies of -308A and -238A in the silicosis group and each subgroup were similar to those in the normal group (P <0.01). The distribution frequency of TNF-α-308A in 140 elderly silicosis patients was much lower than that of the normal control group (P <0.001). Conclusions The base mutation of G → A at TNF-α-308 and -238 sites is related to the occurrence and severity of silicosis in Han Chinese in Southwest China. TNF-α may affect the prognosis and survival of patients with silicosis.