肿瘤坏死因子-α及其Ⅱ型受体基因多态性与煤工尘肺

Potential effect of tumor necrosis factor-α and its receptor Ⅱ gene polymorphisms on the pathogenesis of coal worker's pneumoconiosis

目的 探讨肿瘤坏死因子 α(TNF α)及其Ⅱ型受体 (TNFRⅡ )基因多态性在煤工尘肺发病遗传易感性中的作用及其与煤工尘肺纤维化程度的联系。方法 选择 2 34例汉族煤工尘肺患者和4 4 0例煤尘接触者为研究对象 ,拍摄高仟伏X射线后前位胸片 ,按尘肺病诊断标准进行诊断和分期 ;采集研究对象的外周静脉血 ,应用多聚酶链反应 -限制片段长度多态性 (PCR RFLP)技术检测其TNF α及TNFRⅡ基因多态性。结果 TNF α - 30 8位点G A +A A基因型和TNFRⅡ 196位点T G +G G基因型分布频率在成组或 1∶1配对分析中 ,煤工尘肺患者和煤尘接触者两组间差异均无显著性 (P >0 .0 5 )。G A +A A基因型频率在Ⅲ期煤工尘肺患者中为 2 0 .0 0 % ,高于煤尘接触者 (10 .91% )、Ⅰ期(10 .34% )和Ⅱ期煤工尘肺患者 (7.5 0 % ) ;1∶1配对后 ,G A +A A基因型携带者发展成Ⅲ期煤工尘肺的危险性是G G基因型的 3倍 (95 %CI:0 .35～ 2 5 .84 )。结论 TNF α和TNFRⅡ基因多态性在汉族煤工尘肺发病的遗传易感性中不起主要作用。TNF α基因多态性可能与煤工尘肺纤维化严重程度相关。

Objective To approach the effect of tumor necrosis factor-α(TNF-α) and tumor necrosis factor receptor Ⅱ(TNFRⅡ) gene polymorphisms on genetic susceptibility of coal worker's pneumoconiosis and their relationship with pulmonary fibrosis. Methods Two hundred and thirty-four cases of coal worker's pneumoconiosis(CWP) and four hundred and forty coal mine workers(controls) were selected,and the cases of CWP were divided into three subgroups based on the various stages of Ⅰ,Ⅱ and Ⅲ.3 ml peripheral vein blood was drawn from every subject.Using polymerase chain reaction-restriction fragment length polymorphisms(PCR-RFLP) techniques,TNF-α and TNFRⅡ gene polymorphisms were analyzed. Results In both group matching and 1∶1 paired matching,there was no significant difference between CWP workers and controls in distribution frequencies of G/A+A/A(TNF-α -308) and T/G+G/G(TNFRⅡ 196) genotypes.The distribution frequency of G/A+ A/A genotype in CWP with stage Ⅲ(20.00%)was higher than those in control(10.91%),and CWP cases with stage Ⅰ (10.34%) and Ⅱ(7.50%) respectively.The risk of CWP with stage Ⅲ in those with G/A+A/A genotype was 2-fold higher than with G/G genotype(OR=3.00,95% CI:0.35～25.84) for 1∶1 paired matching. Conclusions TNF-α and TNFRⅡ gene polymorphisms does not play an important role in susceptibility to CWP of Han race.TNF-α gene promoter polymorphisms might be related with the degree of severe pulmonary fibrosis in CWP.