Genetic polymorphisms influencing arsenic metabolism: evidence from Argentina.
Genetic polymorphisms influencing arsenic metabolism: evidence from Argentina.
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DOI：
10.1289/ehp.9734
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发表时间：
2007-04
影响因子：
10.4
通讯作者：
Vahter M
中科院分区：
文献类型：
--
作者：
Schläwicke Engström K;Broberg K;Concha G;Nermell B;Warholm M;Vahter M
砷引起的疾病的易感性个体之间差异很大，可能是由于个体间的变化，影响有毒代谢产物的保留和分布的As代谢。为了阐明遗传因素在As代谢中的作用，我们研究了6个基因的多态性如何影响北方阿根廷一组土著妇女（n = 147）的尿代谢产物模式，这些妇女在饮用水中暴露于约200 μg/L As。这些妇女的尿中甲基化砷（MMA）的百分比较低，二甲基化砷（DMA）的百分比较高。MMA与不良健康影响有关，DMA的代谢物体内保留最低。研究的基因是砷（+III）甲基转移酶（AS 3 MT），谷胱甘肽S-转移酶ω 1（GSTO 1），5-甲基四氢叶酸-高半胱氨酸甲基转移酶（MTR），亚甲基四氢叶酸还原酶（MTHFR），谷胱甘肽S-转移酶μ 1（GSTM 1）和θ 1（GSTT 1）。我们发现AS 3 MT的三个内含子多态性（G12390 C、C14215 T和G35991 A）与尿液中较低的MMA百分比（%MMA）和较高的DMA百分比（%DMA）相关。与野生型纯合子相比，变异纯合子显示约一半的%MMA。这些多态性与其他群体有很强的连锁关系，等位基因频率较高（72-76%）。我们还在多变量回归分析中看到其他多态性的微小影响，对GSTM 1（影响%MMA）和GSTT 1（影响%MMA和%DMA）的缺失基因型进行了影响修改。对于孕妇，叶酸代谢基因MTR和MTHFR的影响修饰。总之，这些研究结果表明，多态性AS 3 MT和可能的GSTM 1，GSTT 1，MTR，MTHFR是负责的大部分个体间变异的代谢和易感性。
The susceptibility to arsenic-induced diseases differs greatly between individuals, possibly due to interindividual variations in As metabolism that affect retention and distribution of toxic metabolites. To elucidate the role of genetic factors in As metabolism, we studied how polymorphisms in six genes affected the urinary metabolite pattern in a group of indigenous women (n = 147) in northern Argentina who were exposed to approximately 200 μg/L As in drinking water. These women had low urinary percentages of monomethylated As (MMA) and high percentages of dimethylated As (DMA). MMA has been associated with adverse health effects, and DMA has the lowest body retention of the metabolites. The genes studied were arsenic(+III)methyltransferase (AS3MT), glutathione S-transferase omega 1 (GSTO1), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), methylenetetrahydrofolate reductase (MTHFR), and glutathione S-transferases mu 1 (GSTM1) and theta 1 (GSTT1). We found three intronic polymorphisms in AS3MT (G12390C, C14215T, and G35991A) associated with a lower percentage of MMA (%MMA) and a higher percentage of DMA (%DMA) in urine. The variant homozygotes showed approximately half the %MMA compared with wild-type homozygotes. These polymorphisms were in strong linkage, with high allelic frequencies (72–76%) compared with other populations. We also saw minor effects of other polymorphisms in the multivariate regression analysis with effect modification for the deletion genotypes for GSTM1 (affecting %MMA) and GSTT1 (affecting %MMA and %DMA). For pregnant women, effect modification was seen for the folate-metabolizing genes MTR and MTHFR. In conclusion, these findings indicate that polymorphisms in AS3MT—and possibly GSTM1, GSTT1, MTR, and MTHFR—are responsible for a large part of the interindividual variation in As metabolism and susceptibility.
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影响因子：
5.1
作者：
MARAFANTE, E;VAHTER, M;ENVALL, J
通讯作者：
ENVALL, J
影响因子：
10.4
作者：
Concha, G;Nermell, B;Vahter, M
通讯作者：
Vahter, M
影响因子：
10.4
作者：
Chung JS;Kalman DA;Moore LE;Kosnett MJ;Arroyo AP;Beeris M;Mazumder DN;Hernandez AL;Smith AH
通讯作者：
Smith AH
影响因子：
4.1
作者：
Marnell, LL;Garcia-Vargas, GG;Aposhian, HV
通讯作者：
Aposhian, HV
DOI：
10.1016/s1383-5742(97)00005-7
发表时间：
1997-06-01
影响因子：
5.3
作者：
Chiou, HY;Hsueh, YM;Chen, CJ
通讯作者：
Chen, CJ