Custodio Hipolito M, Broberg Karin, Wennberg Maria, Jansson Jan-Håkan, Vessby Bengt, Hallmans Göran, Stegmayr Birgitta, Skerfving Staffan
Department of Occupational and Environmental Medicine, Lund University Hospital, Lund, Sweden.
Arch Environ Health. 2004 Nov;59(11):588-95. doi: 10.1080/00039890409603438.
Methylmercury is eliminated from the human body as glutathione (GSH) conjugates. GSH production is mediated by glutamyl-cysteine ligase (GCL) and conjugation by glutathione S-transferases (GST). In this study, the authors tested whether polymorphisms in GCL and GST genes modify methylmercury retention. Erythrocyte mercury concentration (EryHg), plasma polyunsaturated fatty acids (PPUFA), and genotype for GCLC, GCLM, GSTA1, GSTM1, GSTP1, and GSTT1 were determined in 365 individuals. A general linear model was developed for analyzing whether genotype modified the regression of EryHg on PPUFA. The presence of one variant allele for either GCLC-129 or GSTP1-114 was associated with higher EryHg and steeper regression slope. No similar trends were shown for GCLM, GSTA1, GSTM1, or GSTT1. These findings indicate that GCLC polymorphisms that affect GSH production also affect methylmercury retention, and that GSTP1 may play a role in conjugating methylmercury with GSH.
甲基汞以谷胱甘肽（GSH）结合物的形式从人体中排出。谷胱甘肽的产生由谷氨酰半胱氨酸连接酶（GCL）介导，结合过程则由谷胱甘肽S-转移酶（GST）完成。在本研究中，作者测试了GCL和GST基因的多态性是否会改变甲基汞的潴留情况。测定了365名个体的红细胞汞浓度（EryHg）、血浆多不饱和脂肪酸（PPUFA）以及GCLC、GCLM、GSTA1、GSTM1、GSTP1和GSTT1的基因型。建立了一个通用线性模型，用于分析基因型是否会改变EryHg对PPUFA的回归关系。GCLC - 129或GSTP1 - 114存在一个变异等位基因与较高的EryHg和更陡的回归斜率相关。GCLM、GSTA1、GSTM1或GSTT1未显示出类似趋势。这些发现表明，影响谷胱甘肽产生的GCLC多态性也会影响甲基汞的潴留，并且GSTP1可能在甲基汞与谷胱甘肽的结合过程中发挥作用。
