Public Health Research Group, School of Dentistry, Campus of Zaragocilla, University of Cartagena, Cartagena 130015, Colombia; Environmental Chemistry Research Group, School of Exact and Natural Sciences, Campus of San Pablo, University of Cartagena, Cartagena 130015, Colombia.
Center for Research in Sustainable Chemistry, CIQSO, University of Huelva, Huelva 21071, Spain.
Chemosphere. 2018 Dec;212:927-936. doi: 10.1016/j.chemosphere.2018.08.139. Epub 2018 Aug 28.
This study assessed the effects of polymorphic variants of gutathione-S-transferase and metallothioneins on profiles of urinary arsenic species. Drinking groundwater from Margarita and San Fernando, Colombia were analyzed and the lifetime average daily dose (LADD) of arsenic was determined. Specific surveys were applied to collect demographic information and other exposure factors. In addition, GSTT1-null, GSTM1-null, GSTP1-rs1695 and MT-2A-rs28366003 genetic polymorphisms were evaluated, either by direct PCR or PCR-RFLP. Urinary speciated arsenic concentrations were determined by HPLC-HG-AFS for species such as As, As, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and total urinary As (TuAs). Primary methylation index (PMI) and secondary methylation index (SMI) were also calculated as indicators of the metabolic capacity. Polymorphisms effects were tested using multivariate analysis, adjusted by potential confounders. The As concentrations in groundwater were on average 34.6 ± 24.7 μg/L greater than the WHO guideline for As (10 μg/L). There was a correlation between As concentrations in groundwater and TuAs (r = 0.59; p = 0.000). Urinary inorganic arsenic (%InAs) was associated with GSTP1, LADD, GSTP1Age, GSTP1alcohol consumption (r = 0.43; likelihood-ratio test, p = 0.000). PMI was associated with sex (r = 0.20; likelihood-ratio test, p = 0.007). GSTP1 (AG + GG) homozygotes/heterozygotes could increase urinary %InAs and decrease the PMI ratio in people exposed to low and high As from drinking groundwater. Therefore, the explanatory models showed the participation of some covariates that could influence the effects of the polymorphisms on these exposure biomarkers to As.
本研究评估了谷胱甘肽-S-转移酶和金属硫蛋白的多态性变异对尿砷形态的影响。对来自哥伦比亚玛格丽塔和圣费尔南多的地下水进行了分析，并确定了砷的终生平均日剂量（LADD）。还进行了专门的调查，以收集人口统计学信息和其他暴露因素。此外，评估了 GSTT1-缺失、GSTM1-缺失、GSTP1-rs1695 和 MT-2A-rs28366003 遗传多态性，通过直接 PCR 或 PCR-RFLP 进行。通过 HPLC-HG-AFS 测定尿砷形态，测定砷、砷、一甲基砷酸（MMA）、二甲基砷酸（DMA）和总尿砷（TuAs）等物质的浓度。还计算了初级甲基化指数（PMI）和次级甲基化指数（SMI），作为代谢能力的指标。通过多元分析测试了多态性的影响，并通过潜在的混杂因素进行了调整。地下水砷浓度比世界卫生组织砷（10μg/L）指导值平均高出 34.6±24.7μg/L。地下水砷浓度与 TuAs 呈正相关（r=0.59；p=0.000）。尿无机砷（%InAs）与 GSTP1、LADD、GSTP1年龄、GSTP1饮酒量呈正相关（r=0.43；似然比检验，p=0.000）。PMI 与性别呈正相关（r=0.20；似然比检验，p=0.007）。GSTP1（AG+GG）纯合子/杂合子可能会增加接触低浓度和高浓度地下水的人群的尿%InAs，降低 PMI 比值。因此，解释模型表明，一些混杂因素的参与可能会影响多态性对这些砷暴露生物标志物的影响。
