凋亡信号通路基因多态性与煤工尘肺易感性  

Polymorphisms in Fas pathway genes and risk of coal worker pneumoconiosis

作　　者：王莎莎[1] 叶洋[1] 钱海洋[1] 宋志方 贾晓民 倪春辉[1] 

机构地区：[1]南京医科大学公共卫生学院职业医学与环境卫生学系,南京210029 [2]徐州矿务集团总医院,南京210029

出　　处：《中华劳动卫生职业病杂志》2011年第10期756-760,共5页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家自然基金面上项目（30872093）

摘　　要：目的 探讨凋亡信号通路基凶细胞凋亡基因（FAS）、FAS配体基凶（FASL）、半胱氨酸一天冬氨酸蛋白质酶（CASP8）及CASP3单核苷酸多态性（SNP）与煤T尘肺易感性的关系。方法 采用病例一对照的研究方法，选择511例煤工尘肺患者为病例组，530例同单位、间T种、且T：龄相近、未患尘肺的煤尘接触者为对照组；聚合酶链反应一限制性片段长度多态性（PCR-RFLP）法检测5个SNP位点的基因型；CASP3rs6948位点用荧光定量PCR法进行基因分型。结果煤工尘肺组和对照组6个多态性位点的各基因型的分布频率比较，差异无统计学意义（P〉O.05）。CASP8—652位点的6个碱基缺失（DD型）可明显增加煤工尘怖患病的危险性（调整后OR=1.96，95％CI=1.15～3.33，P=0．013），其他各基因型对煤T尘肺患病危险性没有明显的影响；对CASP8-652I〉D基凶多态性进行分层分析发现，工龄≥28年组、吸烟组及I期煤工尘肺携带CASP8-652DD基因型者煤T尘肺的患病危险性明显增高，差异有统计学意义（P〈0．05）。6个多态性位点不同基因型之间的相互作用与煤T尘肺患病的关联性分析发现，携带FAS-1377GG／CASP8-652DD型者、携带FAS-670AG／CASP8-652DD型者和携带FASL-844CT／CASP8-652DD型者煤T尘肺患病危险性明显增加；携带FAS-1377GA／CASP8-6521D型者煤丁尘肺患病危险性明显降低。对I期煤T尘肺患者中CASP8-652位点II、ID、DD3种基因型携带者发病前的粉尘暴露时间进行回归分析，差异无统计学意义（P〉0．05）。I期煤工尘肺患者中不同基冈型携带者发病前的粉尘暴露时间比较，差异无统计学意义（P〉O．05）。结论 CASP8—652缺失基因型在煤T尘肺病变的发腱过程中可能起一定的作崩，并且与FAS-1377、FAS-670及FAL-844存在基冈相互作用。Objective To explore the possible association between six single nucleotide polymor- phisms （SNPs） of Fas pathway genes aml the risks of coal worker pneumoconiosis （GWP）. Methods This case- control study consisted of 511 male patients with CWP and 530 male controls from the same coal mines. Five SNPs of Fas pathway genes were detected by restriction fragment length polymorphisms （PCR-RFLP） and CASP3 （rs6948） was genotyped by quantitative real-time polymerase chain reaction （qRT-PCR）. Results There were no differences of genotype frequencies of 6 SNPs between cases with CWP and controls. A significant in- creased risk of CWP was found in subjects with CASP8-652DD genotype as compared to subjects with CASP8- 652II genotype （P〈0.05）, and the further stratification analysis showed that smoking cases with CWP stage I, long exposure time and CASP8-652DD genotype had high risk of CWP （P〈0.05）. The analysis of gene-gene in- teractions indicated that the carriers with FAS-1377GG/ CASPS-652DD, FAS-670AG/CASP8-652DD and FASL-844CT/CASP8-652DD had the increased risk of CWP, and the carriers with FAS-1377GA/CASP8-652ID had the reduced risk of CWP. There were no significant differences of exposure times among the cases with CWP stage I and 3 genotypes of CASPS-652. Conclusion CASP8-652 6N DD genotype may play a role in CWP de- velopment and interact with SNPs of FAS-1377, FAS-670 and FASL-844.

关 键 词：尘肺 多态性 单核苷酸 疾病易感性 

分 类 号：R1[医药卫生—公共卫生与预防医学]