微粒体环氧化物水解酶基因多态性与煤工尘肺易感性

Gene variance in microsomal epoxide hydrolase and the susceptibility of coal workers＇ pneumoconiosis

目的探讨微粒体环氧化物水解酶（EPHX1）基因单核苷酸多态性（SNPs）与煤工尘肺易感性的关系。方法应用病例-对照的研究方法，以697例煤工尘肺患者为病例组，694例同单位、同工种、无尘肺的煤尘接触者为对照组；采用高千伏胸部x射线和体格检查确定病例和对照；采取外周静脉血，苯酚-氯仿萃取分离蛋白质，乙醇沉淀法提取DNA；根据中国人群HapMap database数据库查找SNP位点，采用ABI 7900实时PCR系统（Applied Biosystems，Foster City，CA，USA）对3个SNP位点进行基因型分型，用SDS等位基因分型软件来处理基因分型的结果。结果3个SNP位点的基因型分布频率中，仅EPHX1（rs2234922）病例组和对照组在共显性模型（OR=0．22，95％CI=0．06-0．79，P=0．020）、隐性模型（OR=0．23，95％CI=0．06—0．82，P=0．023）及相加模型（OR=0．75,95％C／=0．58—0．96，P=0．022）中的差异有统计学意义；对工龄和吸烟进行进一步的分层分析，发现不吸烟者携带EPHX1（rs2234922）GG基因型发生煤工尘肺的危险性明显降低（OR=0．10，95％CI=0．01—0．83，P=0．033）。结论EPHX1（rs2234922）位点GG基因型降低了尘肺的易感性，在尘肺的发生发展中可作为一个保护性因素。

Objective To explore whetherthe tagging single nucleotide polymorphisms （SNPs） within EPHX1 gene were involved in the genetic susceptibility to coal worker＇s pneumoconiosis （CWP） by casecontrol study. Methods This study consisted of 697 CWP patients and 694 controls. All the subjects were Han Chinese, underground coal miners and recruited from coal mines of Xuzhou Mining Business Group Co Ltd.. The venous blood samples were obtained from all subjects and extracted genome DNA from the isolated leucocytes. Three SNPs were selected from the HapMap and the genotyping was done by the TaqMan method with the ABI 7900HT Real Time PCR system. Results The Single SNP analyses showed that the genotype frequencies of EPHX1 （rs2234922） was significantly associated with decreased risk of CWP under co-dominant model （OR= 0.22, 95%CI=0.06-0.79, P=0.020）, recessive model （OR=0.23, 95%CI=0.06-0.82, P=0.023）, and addictive model （OR=0.75, 95%CI=0.58-0.96, P=-0.022）. The further stratification analysis showed that the risk of CWP will significantly decreased in non-smoking groups （OR=0.10, 95%CI=0.01-0.83, P=0.033）. Conclusions Our results suggest that individuals with the EPHX1 （rs223492） GG genotype was associated with a dereased risk of CWP, and it has a protective effect on the developing CWP.