肿瘤坏死因子-α及其Ⅱ型受体基因多态性与煤工尘肺的遗传易感性

Study of TNF-α and TNFR Ⅱ Gene Polymorphisms and Coal Workers Pneumoconiosis Genetic Susceptibility

[目的]探讨肿瘤坏死因子-α(TNF-α)基因-308位点、肿瘤坏死因子Ⅱ型受体(TNFRⅡ)基因196位点的基因多态性与煤工尘肺病遗传易感性的关系。[方法]采用病例对照研究方法,选择接尘工龄大于1年,无免疫系统疾病史, 除尘肺患者外,对照组接触工人无肺部疾病史,以问卷调查和现场体检方式收集职业接触史、既往病史、家族史和尘肺诊断史,采集每个研究对象静脉血3 ml,采用盐析法从外周静脉血的有核细胞中提取DNA。按文献报道的合成序列引物、采用PCR扩增反应和RFLP技术分析TNF-α和TNFRⅡ。[结果]TNF-α-308位点G/A+A/A基因型和TNFRⅡ196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>0.05)。G/A+A/A 基因型频率在Ⅲ期煤工尘肺患者中为20.00%,高于煤尘接触者(10.91%)、Ⅰ期(10.34%)和Ⅱ期煤工尘肺患者(7.50%);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:0.35-25.84)。[结论]TNF-α基因-308位点和TNFRⅡ基因196位点多态性在中国汉族煤工尘肺发病的遗传易感因素中不起主要作用。TNF-α基因-308 位点多态性可能与煤工尘肺重度纤维化相关联,值得进一步研究证实;TNFRⅡ基因196位点与煤工尘肺纤维化程度无关。

[Objective] To approach the role of tumor necrosis factor-α （ TNF-α） and tumor necrosis factor receptor Ⅱ （ TNFR Ⅱ ） gene polymorphisms in genetic susceptibility to coal worker＇s pneumoconiosis.[ Methods] A case-control study was conducted .Coal workers with pneulnoconiosis （ CWP ） with more than one year working duration without immune system diseases were selected , coal mine workers without pulmonary diseases were selected as controls. Gathering the history information of disease, occupation and family by questionaire investigation and physical examination were conducted. 3 ml peripheral vein blood was drawn from each subject. Sequence specific primers were synthesized according to literature. Using polymerase chain reaction-restriction fragment length polymorphisms （ PCR-RFLP ） methodology, TNF-α and TNFR Ⅱ gene polymorphisms were analyzed. [ Results] In both groups matching and 1：1 paired matching, there was no significant difference between cases with CWP and workers in the control group in distribution frequencies of G/A＋A/A （ TNF-α-308 ） and T/G＋G/G （ TNFR Ⅱ 196 ） gcnotypes. The distribution frequency of G/A＋A/A genotype in CWP with stage Ⅲ was 20.00%, higher than those in the control group （ 10.91% ）, and eases 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 3 folds higher than with G/G genotype （ OR=3.00, 95% CI： 0.35-25.84 ） for 1：1 paired matching. [ Conclusions] TNF-α and TNFR Ⅱ gene polymorphisms didn＇t play an important role in susceptibility to CWP in Han race. TNF-α gene promoter polymorphisms might he related with the development of severe pulmonary fibrosis in CWP, and TNFR Ⅱ gene polymorphisms have nothing with the degree of pulmonary fibrosis.