Genetic polymorphisms in glutathione S-transferase (GST) superfamily and arsenic metabolism in residents of the Red River Delta, Vietnam
Genetic polymorphisms in glutathione S-transferase (GST) superfamily and arsenic metabolism in residents of the Red River Delta, Vietnam
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DOI：
10.1016/j.taap.2009.11.007
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发表时间：
2010-02-01
影响因子：
3.8
通讯作者：
Tanabe, Shinsuke
中科院分区：
文献类型：
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作者：
Agusa, Tetsuro;Iwata, Hisato;Tanabe, Shinsuke
为了阐明遗传因素在砷代谢中的作用，我们研究了谷胱甘肽S-转移酶（GST）超家族成员的遗传多态性与越南红河三角洲居民头发和尿砷浓度以及尿砷谱的关系。对CST omega 1（GSTO 1）A1 a140 Asp、Glu 155 del、Glu 208 Lys、Thr 217 Asn和Ala 236 Val、GST omega 2（GSTO 2）Asn 142 Asp、CST pi 1（GSTP 1）Ile 105 Val、GST mu 1（GSTM 1）野生型/无效和GST theta 1（GSTT 1）野生型/无效进行基因分型。GSTO 1 Glu 208 Lys、Thr 217 Asn和Ala 236 Val在该群体中未发现突变等位基因。GSTO 1 Glu 155 del杂合子尿As-V浓度高于野生型。GSTM 1野生型的尿中DMA（V）的百分比高于GSTM 1缺失型。在这项研究中观察到的GSTP 1 Ile 105 Val和砷暴露水平和配置文件之间的强相关性。尤其是GSTP 1 Ile 105 Val杂合子具有较高的无机砷向单甲基砷的代谢能力，而As-V向As-III的代谢能力则相反。此外，其他因素，包括性别，年龄，体重指数，饮用水中的砷水平，和基因型的砷（+ 3氧化态）甲基转移酶（AS 3 MT）也显着相关的砷水平和配置文件在越南。据我们所知，这是第一个研究表明，在越南人群中的砷代谢的CST超家族的遗传因素的关联。(C)2009 Elsevier Inc. All rights reserved.
To elucidate the role of genetic factors in arsenic metabolism, we investigated associations of genetic polymorphisms in the members of glutathione S-transferase (GST) superfamily with the arsenic concentrations in hair and urine, and urinary arsenic profile in residents in the Red River Delta, Vietnam. Genotyping was conducted for CST omega 1 (GSTO1) A1a140Asp, Glu155del, Glu208Lys, Thr217Asn, and Ala236Val, GST omega 2 (GSTO2) Asn142Asp, CST pi 1 (GSTP1) Ile105Val, GST mu 1 (GSTM1) wild/null, and GST theta 1 (GSTT1) wild/null. There were no mutation alleles for GSTO1 Glu208Lys, Thr217Asn, and Ala236Val in this population. GSTO1 Glu 155del hetero type showed higher urinary concentration of As-V than the wild homo type. Higher percentage of DMA(V) in urine of GSTM1 wild type was observed compared with that of the null type. Strong correlations between GSTP1 Ile105Val and arsenic exposure level and profile were observed in this study. Especially, heterozygote of GSTP1 Ile105Val had a higher metabolic capacity from inorganic arsenic to monomethyl arsenic, while the opposite trend was observed for ability of metabolism from As-V to As-III. Furthermore, other factors including sex, age, body mass index, arsenic level in drinking water, and genotypes of As (+ 3 oxidation state) methyltransferase (AS3MT) were also significantly co-associated with arsenic level and profile in the Vietnamese. To our knowledge, this is the first study indicating the associations of genetic factors of CST superfamily with arsenic metabolism in a Vietnamese population. (C) 2009 Elsevier Inc. All rights reserved.