Yang Pan, Zeng Qiang, Cao Wen-Cheng, Wang Yi-Xin, Huang Zhen, Li Jin, Liu Chong, Lu Wen-Qing
Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Environ Res. 2016 May;147:445-52. doi: 10.1016/j.envres.2016.03.009. Epub 2016 Mar 10.
Trihalomethanes (THMs) have been reported to be associated with altered semen quality, and this association may be modified by inherited differences in cytochrome P450 (CYP2E1) and glutathione S-transferase (GSTZ1 and GSTT1), which metabolize THMs. We conducted a cross-sectional study to examine the interactions between CYP2E1, GSTZ1 and GSTT1 polymorphisms and exposure to THMs on semen quality among 401 men from the Reproductive Center of Tongji Hospital in Wuhan China. The baseline blood concentrations of four individual THMs, chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM) and bromoform (TBM), were measured as biomarkers of exposure to drinking water THMs. Genotypes were determined by real-time PCR, and semen-quality parameters were evaluated according to the World Health Organization guidelines. GSTT1 genotype significantly modified the association between exposure to Br-THMs (sum of BDCM, DBCM and TBM) and below-reference sperm motility (Pint=0.02). Men with above-median blood Br-THM levels had an increased odds ratio (OR) of below-reference sperm compared to men with below-median blood Br-THM levels (OR=2.15, 95% CI: 1.11, 4.19) in the GSTT1 null genotype only. In addition, we found that men with a TT of CYP2E1 rs 915,906 had higher blood TCM and TTHM (sum of TCM, BDCM, DBCM and TBM) concentrations than men with a CT/CC of CYP2E1 rs 915,906. Our results suggest that GSTT1 polymorphisms modify Br-THM exposure relation with semen quality, and CYP2E1 polymorphisms are associated with internal levels of exposure to THMs.
据报道，三卤甲烷（THMs）与精液质量改变有关，而这种关联可能会因细胞色素P450（CYP2E1）以及参与THMs代谢的谷胱甘肽S-转移酶（GSTZ1和GSTT1）的遗传差异而改变。我们进行了一项横断面研究，以探讨中国武汉同济医院生殖中心401名男性中CYP2E1、GSTZ1和GSTT1基因多态性与THMs暴露对精液质量的相互作用。测量了四种单个THMs（氯仿（TCM）、溴二氯甲烷（BDCM）、二溴氯甲烷（DBCM）和溴仿（TBM））的基线血浓度，作为饮用水中THMs暴露的生物标志物。通过实时PCR确定基因型，并根据世界卫生组织指南评估精液质量参数。GSTT1基因型显著改变了Br-THMs（BDCM、DBCM和TBM之和）暴露与低于参考值的精子活力之间的关联（交互P值=0.02）。仅在GSTT1无效基因型中，血Br-THM水平高于中位数的男性与血Br-THM水平低于中位数的男性相比，低于参考值精子的比值比（OR）增加（OR=2.15，95%CI：1.11，4.19）。此外，我们发现CYP2E1 rs915906为TT基因型的男性比CYP2E1 rs915906为CT/CC基因型的男性血TCM和总THMs（TCM、BDCM、DBCM和TBM之和）浓度更高。我们的结果表明，GSTT1基因多态性改变了Br-THMs暴露与精液质量的关系，而CYP2E1基因多态性与THMs的体内暴露水平有关。
