Genetic polymorphisms in AS3MT and arsenic metabolism in residents of the Red River Delta, Vietnam
Genetic polymorphisms in AS3MT and arsenic metabolism in residents of the Red River Delta, Vietnam
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DOI：
10.1016/j.taap.2009.01.015
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发表时间：
2009-04-15
影响因子：
3.8
通讯作者：
Tanabe, Shinsuke
中科院分区：
文献类型：
--
作者：
Agusa, Tetsuro;Iwata, Hisato;Tanabe, Shinsuke
为了阐明遗传因素在砷（As）代谢中的作用，我们研究了越南红河三角洲居民头发和尿液中As浓度以及尿液As谱与As（+3氧化态）甲基转移酶（AS3MT）单核苷酸多态性（snp）的关系。地下水中总砷含量为0.7 ~ 502 μ g/l。采用砂滤后，地下水中总砷含量显著降低，表明砂滤能有效去除原水中的砷。男性尿液中无机砷（IAs）浓度和毛发中总砷（As）浓度均高于女性。单甲基larsonic acid (MMA)/IAs与女性年龄显著正相关，表明年龄越大的女性从IAs到MMA的甲基化能力越高。男性体重指数与尿砷浓度呈负相关。单核苷酸多态性4602AA、35991GG和37853GG的纯合子具有较强的连锁不平衡（LD），其尿中二甲基larsinic酸（DMA）的百分比（%）较高。单核苷酸多态性;4740和12590有强烈的LD并与尿%DMA相关。虽然SNPs 6144、12390、14215和35587组成LD簇，但SNPs 12390GG和35587CC的纯合子在尿液中的DMA/MMA较低，表明这些SNPs在人属类型中从MMA到DMA的甲基化能力较低。SNPs 5913和8973分别与%MMA和%DMA相关。SNP 14458TC杂合子的尿MMA/IAs高于TT纯合子，说明杂合子可能具有更强的IAs甲基化能力。据我们所知，这是第一次研究遗传因素与越南As代谢的关系。(C) 2009爱思唯尔公司版权所有。
To elucidate the role of genetic factors in arsenic (As) metabolism, we studied associations of single nucleotide polymorph isms (SNPs) in As (+3 oxidation state) methyltransferase (AS3MT) with the As concentrations in hair and urine, and urinary As profile in residents in the Red River Delta, Vietnam. Concentrations of total As in groundwater were 0.7-502 mu g/l. Total As levels in groundwater drastically decreased by using sand filter, indicating that the filter could be effective to remove As from raw groundwater. Concentrations of inorganic As (IAs) in urine and total As in hair of males were higher than those of females. A significant positive correlation between monomethylarsonic acid (MMA)/IAs and age in females indicates that older females have higher methylation capacity from IAs to MMA. Body mass index negatively correlated with urinary As concentrations in males. Homozygote for SNPs 4602AA, 35991GG, and 37853GG, which showed strong linkage disequilibrium (LD), had higher percentage (%) of dimethylarsinic acid (DMA) in urine. SNPs; 4740 and 12590 had strong LD and associated with urinary %DMA. Although SNPs 6144, 12390, 14215, and 35587 comprised LD cluster, homozygotes in SNPs 12390GG and 35587CC had lower DMA/MMA in urine, suggesting low methylation capacity from MMA to DMA in homo types for these SNPs. SNPs 5913 and 8973 correlated with %MMA and %DMA, respectively. Heterozygote for SNP 14458TC had higher MMA/IAs in urine than TT homozygote, indicating that the heterozygote may have stronger methylation ability of IAs. To our knowledge, this is the first study on the association of genetic factors with As metabolism in Vietnamese. (C) 2009 Elsevier Inc. All rights reserved.