Department of Paediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region; CUNY School of Public Health and Health Policy, NY, USA.
Environ Res. 2020 Aug;187:109703. doi: 10.1016/j.envres.2020.109703. Epub 2020 May 20.
Genetic variations in glutathione (GSH)-related and metallothionein (MT) genes, which are involved in producing enzymes in the methylmercury (MeHg) metabolism pathway, have been proposed as one of the reasons for the individual variability in MeHg toxicokinetics.
To investigate the impact of genetic variations in MT and GSH-related genes on the association of fish consumption with body burden of MeHg, as measured by hair Hg concentrations among young children and women of childbearing age.
A total of 179 unrelated children and 165 mothers with either high or low fish consumption were recruited from the community. Their hair total Hg (tHg) and MeHg levels and genotypes for SNPs located on the GCLC, GCLM, GPX1, GSTA1, GSTP1, MT1A, MT2A, and MT4 genes were determined. Based on their 14-day food records, the amounts of fish consumed and their MeHg intakes were estimated. The impact of genetic variations on hair Hg concentrations was examined by using Mann-Whitney tests and multivariable linear regression analyses.
The presence of minor alleles of GCLC-129 (rs17883901), GPX1-198 (rs1050450) and MT1M (rs9936741) were associated with significantly lower hair tHg levels in mothers whereas mothers with minor alleles of GSTP1-105(rs1695) and MT1M (rs2270836) have significantly higher hair tHg levels. After adjustment for fish consumption and other confounding factors, apart from MT1M (rs2270836), all of the above SNPs remain significant in the multivariable linear regression models.
Our results in a group of children and women show that genetic variants of GSH-related and MT genes are associated with hair Hg concentrations. These genetic variations are likely to significantly affect MeHg metabolism and thus influence the accumulation of Hg in the human body.
谷胱甘肽（GSH）相关和金属硫蛋白（MT）基因中的遗传变异，这些基因参与甲基汞（MeHg）代谢途径中酶的产生，被认为是 MeHg 毒代动力学个体差异的原因之一。
研究 MT 和 GSH 相关基因的遗传变异对鱼类消费与幼儿和育龄妇女发汞浓度（头发中 Hg 浓度）之间关系的影响。
从社区中招募了 179 名无血缘关系的儿童和 165 名高或低鱼类消费的母亲。测定了他们的头发总汞（tHg）和 MeHg 水平以及位于 GCLC、GCLM、GPX1、GSTA1、GSTP1、MT1A、MT2A 和 MT4 基因上 SNP 的基因型。根据他们的 14 天食物记录，估计了鱼类的摄入量及其 MeHg 摄入量。使用 Mann-Whitney 检验和多变量线性回归分析检查遗传变异对头发 Hg 浓度的影响。
母亲的 GCLC-129（rs17883901）、GPX1-198（rs1050450）和 MT1M（rs9936741）的次要等位基因存在与发 tHg 水平显著降低有关，而 GSTP1-105（rs1695）和 MT1M（rs2270836）的次要等位基因存在与发 tHg 水平显著升高有关。在调整鱼类消费和其他混杂因素后，除了 MT1M（rs2270836）之外，上述所有 SNP 在前多变量线性回归模型中仍然具有统计学意义。
我们在一组儿童和妇女中的研究结果表明，GSH 相关和 MT 基因的遗传变异与发汞浓度有关。这些遗传变异很可能显著影响 MeHg 代谢，从而影响 Hg 在人体内的积累。
