National Center for Birth Defect Monitoring, Department of Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China; Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, Chengdu, Sichuan, China.
Reprod Toxicol. 2021 Dec;106:1-8. doi: 10.1016/j.reprotox.2021.09.010. Epub 2021 Sep 21.
This study aimed to analyze the potential association between trichloroethylene (TCE) exposure and congenital heart disease (CHD) and to explore the effect of metabolic enzyme gene polymorphisms on heart development. A multicenter case-control study was conducted. The trichloroethylene concentrations were measured by UPLC-MSMS in urine. Fourteen SNPs in the GSTA1, GSTP1, MPO, NAT1, NAT2, CYP1A1, CYP1A2, CYP2E1 and EPHX1 genes were genotyped using an improved multiplex ligation detection reaction (iMLDR) technique. A total of 283 cases and 331 controls with maternal urine and/or venous blood were included in the present study. The median NAcDCVC was 7.65 ng/mL in the case group and 7.43 ng/mL in the control group. There was no significant difference in the NAcDCVC concentration between the CHD subtypes and controls (P > 0.05). The GA/AA of GSTA1 rs3957357 could increase the risk of CHDs under the dominant model (aOR = 2.26, 95 % CI: 1.31, 3.90), but other SNPs were not associated with CHDs (P > 0.05). GA or AA genotypes of GSTA1 rs3957357 with lower levels of TCE exposure were 3.53 times at risk relative to mothers carrying the wild type genotype. In conclusion, maternal exposure to trichloroethylene alone is not associated with the occurrence of fetal CHD and CHD subtypes. Maternal GSTA1 rs3957357 may increase the risk of CHD in offspring. TCE exposure and metabolic gene polymorphisms probably interact with each other to induce fetal cardiovascular malformation, but larger sample size studies are needed to confirm this hypothesis.
本研究旨在分析三氯乙烯（TCE）暴露与先天性心脏病（CHD）之间的潜在关联，并探讨代谢酶基因多态性对心脏发育的影响。采用多中心病例对照研究。尿中 TCE 浓度采用 UPLC-MSMS 测定。采用改良多重连接探针扩增反应（iMLDR）技术检测 GSTA1、GSTP1、MPO、NAT1、NAT2、CYP1A1、CYP1A2、CYP2E1 和 EPHX1 基因的 14 个 SNP。共纳入 283 例病例和 331 例对照，包括母亲尿和/或静脉血。病例组和对照组的 NAcDCVC 中位数分别为 7.65ng/ml 和 7.43ng/ml。CHD 各亚型与对照组的 NAcDCVC 浓度无显著差异（P>0.05）。GSTA1 rs3957357 的 GA/AA 基因型可增加 CHD 的发生风险（OR=2.26，95%CI：1.31，3.90），但其他 SNP 与 CHD 无关（P>0.05）。暴露于 TCE 水平较低的 GSTA1 rs3957357 的 GA 或 AA 基因型与携带野生型基因型的母亲相比，风险增加 3.53 倍。结论：母体单独暴露于三氯乙烯与胎儿 CHD 及 CHD 亚型的发生无关。母体 GSTA1 rs3957357 可能增加后代 CHD 的发病风险。TCE 暴露与代谢基因多态性可能相互作用，导致胎儿心血管畸形，但需要更大样本量的研究来验证这一假说。
