孕妇铅镉锰暴露及金属硫蛋白基因多态性与新生儿出生缺陷的关系

目的 探讨铅镉锰暴露及金属硫蛋白基因多态性与新生儿出生缺陷的关系，为出生缺陷的防治以及制定干预措施提供参考依据。方法 本研究采用巢式病例对照研究方法，从广西壮族人群出生队列中选取广西壮族人群聚居的平果、田东、德保、靖西、隆安等县的人民医院及妇幼保健院2015年9月 - 2018年4月期间纳入队列的孕妇作为研究对象。随访收集一般人口学资料、孕期产检资料、出生结局资料等。采用原子吸收分光光度计（石墨炉法）测定孕妇血浆中铅、镉、锰的含量，采用PCR - RFLP法检测金属硫蛋白基因单核苷酸多态性位点。采用多因素logistic回归模型分析孕妇血浆中铅、镉、锰暴露与金属硫蛋白基因多态性与出生缺陷的关系。结果 多因素logistic回归分析显示:孕妇血镉值升高（OR = 1.93,95%CI:1.11～3.36，P＜0.05）、血锰值升高（OR = 1.22,95%CI:1.12～1.34，P＜0.01）、携带MT - 2A rs10636位点突变型基因型（OR = 3.96,95%CI:1.02～15.39，P＜0.05）是出生缺陷发生的危险因素。金属暴露 - 基因多态性交互作用分析结果显示，孕妇锰暴露与MT - 2A rs10636在出生缺陷发生中存在交互作用。结论 镉、锰高暴露、携带MT - 2A rs10636位点突变型基因型可能是出生缺陷发生的危险因素。

Relationship between exposure to lead,cadmium and manganese,metallothionein gene polymorphism and neonatal birth defects in pregnant women

The study aimed to explore the relationship between exposure to lead, cadmium and manganese,metallothionein gene polymorphism and neonatal birth defects, and to provide references for prevention of birth defects and the development of interventions. Methods This study was based on the birth cohort of Guangxi Zhuang population by a nested case-control study. Pregnant women who were enrolled in the People’s Hospital and Maternal and Child Health Hospital of Pingguo, Tiandong, Debao, Jingxi, Longan and other counties in Guangxi from June 2015 to April 2018 were included. Following up was used to collect general demographic data, pregnancy maternity inspection data, birth outcome data, etc. The concentration of lead, cadmium and manganese in maternal plasma was determined by atomic absorption spectrophotometer(graphite furnace method). The single nucleotide polymorphism of metallothionein gene was detected by PCR-RFLP. Statistical analysis was conducted using SPSS22.0 software package. Multivariate logistic regression was used to analyze the relationship between lead, cadmium and manganese exposure, metallothionein gene polymorphism and birth defects in pregnant women. Results Multivariate logistic regression analysis showed that pregnant women had elevated blood cadmium(P<0.05, OR=1.93, 95% CI: 1.11-3.36) and elevated blood manganese(P<0.01, OR=1.22, 95% CI: 1.12-1.34), and carrying the MT-2 A rs10636 site mutation type genotype(P<0.05, OR=3.96, 95% CI: 1.02-15.39) was a risk factor for birth defects. Metal exposure-gene polymorphism interaction analysis showed that there was an interaction between maternal manganese exposure in pregnant women and MT-2 A rs10636 in the occurrence of birth defects. Conclusion High exposure to cadmium and manganese, and the mutant rs10636 locus in MT-2 A gene may be risk factors for birth defects.