As3MT and GST Polymorphisms Influencing Arsenic Metabolism in Human Exposure to Drinking Groundwater
As3MT and GST Polymorphisms Influencing Arsenic Metabolism in Human Exposure to Drinking Groundwater
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DOI：
10.3390/ijms21144832
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发表时间：
2020-07-01
影响因子：
5.6
通讯作者：
Johnson-Restrepo, Boris
中科院分区：
文献类型：
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作者：
Gonzalez-Martinez, Farith;Sanchez-Rodas, Daniel;Johnson-Restrepo, Boris
尿砷代谢产物可能存在个体差异，遗传因素已被报道可以部分解释这种差异。我们评估了砷-3-甲基转移酶和谷胱甘肽-S-转移酶多态性变体对尿砷代谢产物的影响。对哥伦比亚各城市供人类消费的22口地下水威尔斯井进行了分析，以评估终生平均日剂量（拉德）（微克/千克体重/天）的接触情况。调查对象为151名18 ~ 81岁的老年人，收集人口学信息和其他因素。采用真实的PCR和/或常规PCR检测GSTO 2-rs 156697、GSTP 1-rs 1695、As 3 MT-rs3740400、GSTT 1和GSTM 1基因多态性。砷的代谢产物：砷-III，砷-V，一甲基胂酸（MMA），二甲基胂酸（DMA）的测定使用HPLC-HG-AFS。采用多变量分析方法，对多态性变异、拉德和其他因素的影响进行了检验。地下水中总砷浓度的中位数为33.3微克/升，高暴露剂量的拉德中位数为0.33微克/千克体重/天。砷代谢产物和遗传多态性之间的单变量分析显示MMA浓度较高的杂合和/或纯合基因型ofAs 3 MT相比，野生型基因型。此外，与野生型基因型相比，GST 1杂合和/或纯合基因型的DMA浓度较低。GSTM 1缺失基因型的DMA和MMA浓度均高于活性基因型。多变量分析表明，基因-基因和基因-协变量之间的相互作用，以修改MMA和DMA的排泄统计学显着的关联。As 3 MT * GSTM 1和GSTO 2 * GSTP 1多态性之间的相互作用可能是砷尿排泄的潜在调节因子，年龄、拉德和饮酒量等协变量在很大程度上改变了砷暴露人群的个体代谢能力。
The urinary arsenic metabolites may vary among individuals and the genetic factors have been reported to explain part of the variation. We assessed the influence of polymorphic variants of Arsenic-3-methyl-transferase and Glutathione-S-transferase on urinary arsenic metabolites. Twenty-two groundwater wells for human consumption from municipalities of Colombia were analyzed for assessed the exposure by lifetime average daily dose (LADD) (mu g/kg bw/day). Surveys on 151 participants aged between 18 and 81 years old were applied to collect demographic information and other factors. In addition, genetic polymorphisms (GSTO2-rs156697,GSTP1-rs1695,As3MT-rs3740400,GSTT1andGSTM1) were evaluated by real time and/or conventional PCR. Arsenic metabolites: As-III, As-V, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were measured using HPLC-HG-AFS. The influence of polymorphic variants, LADD and other factors were tested using multivariate analyses. The median of total arsenic concentration in groundwater was of 33.3 mu g/L and the median of LADD for the high exposure dose was 0.33 mu g/kg bw/day. Univariate analyses among arsenic metabolites and genetic polymorphisms showed MMA concentrations higher in heterozygous and/or homozygous genotypes ofAs3MTcompared to the wild-type genotype. Besides, DMA concentrations were lower in heterozygous and/or homozygous genotypes ofGSTP1compared to the wild-type genotype. Both DMA and MMA concentrations were higher inGSTM1-nullgenotypes compared to the active genotype. Multivariate analyses showed statistically significant association among interactions gene-gene and gene-covariates to modify the MMA and DMA excretion. Interactions between polymorphic variantsAs3MT*GSTM1andGSTO2*GSTP1could be potential modifiers of urinary excretion of arsenic and covariates as age, LADD, and alcohol consumption contribute to largely vary the arsenic individual metabolic capacity in exposed people.