气候变化领域集成服务门户(CCPortal): AS3MT, GSTO, and PNP polymorphisms: Impact on arsenic methylation and implications for disease susceptibility

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DOI	10.1016/j.envres.2014.03.012
	AS3MT, GSTO, and PNP polymorphisms: Impact on arsenic methylation and implications for disease susceptibility
	Antonelli, Ray 1; Shao, Kan 1; Thomas, David J.2; Sams, Reeder, II 3; Cowden, John 3
发表日期	2014-07-01
ISSN	0013-9351
卷号	132 页码:156-167
英文摘要	Background: Oral exposure to inorganic arsenic (iAs) is associated with adverse health effects. Epidemiological studies suggest differences in susceptibility to these health effects, possibly due to genotypic variation. Genetic polymorphisms in iAs metabolism could lead to increased susceptibility by altering urinary iAs metabolite concentrations. Objective: To examine the impact of genotypic polymorphisms on iAs metabolism. Methods: We screened 360 publications from PubMed and Web of Science for data on urinary mono- and dimethylated arsenic (MMA and DMA) percentages and polymorphic genes encoding proteins that are hypothesized to play roles in arsenic metabolism. The genes we examined were arsenic (+3) methyltransferase (AS3MT), glutathione-s-transferase omega (GSTO), and purine nucleoside phosphoulase (PNP). Relevant data were pooled to determine which polymorphisms are associated across studies with changes in urinary metabolite concentration. Results: In our review, AS3MT polymorphisms rs3740390, rs11191439, and rs11191453 were associated with statistically significant changes in percent urinary MMA. Studies of GSTO polymorphisms did not indicate statistically significant associations with methylation, and there are insufficient data on PNP polymorphisms to evaluate their impact on metabolism. Discussion: Collectively, these data support the hypothesis that AS3MT polymorphisms alter in vivo metabolite concentrations. Preliminary evidence suggests that AS3MT genetic polymorphisms may impact disease susceptibility GSTO polymorphisms were not associated with iAs-associated health outcomes. Additional data are needed to evaluate the association between PNP polymorphisms and iAs-associated health outcomes. Delineation of these relationships may inform iAs mode(s) of action and the approach for evaluating low-dose health effects for iAs. Conclusions: Genotype impacts urinary iAs metabolite concentrations and may be a potential mechanism for iAs-related disease susceptibility. Published by Elsevier Inc.
英文关键词	Arsenic;Arsenic methyltransferase;Purine nucleoside phosphorylase;Glutathione-s-transferase omega;Genetic polymorphisms
语种	英语
WOS记录号	WOS:000337862300023
来源期刊	ENVIRONMENTAL RESEARCH
来源机构	美国环保署
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/62178
作者单位	1.US EPA, ORISE Fellow, Hazardous Pollutant Assessment Grp, Natl Ctr Environm Assessment, Res Triangle Pk, NC 27711 USA; 2.US EPA, Integrated Syst Toxicol Div, Natl Hlth & Environm Res Lab, Res Triangle Pk, NC 27711 USA; 3.US EPA, Hazardous Pollutant Assessment Grp, Natl Ctr Environm Assessment, Res Triangle Pk Div, Res Triangle Pk, NC 27711 USA
推荐引用方式 GB/T 7714	Antonelli, Ray,Shao, Kan,Thomas, David J.,et al. AS3MT, GSTO, and PNP polymorphisms: Impact on arsenic methylation and implications for disease susceptibility[J]. 美国环保署,2014,132:156-167.
APA	Antonelli, Ray,Shao, Kan,Thomas, David J.,Sams, Reeder, II,&Cowden, John.(2014).AS3MT, GSTO, and PNP polymorphisms: Impact on arsenic methylation and implications for disease susceptibility.ENVIRONMENTAL RESEARCH,132,156-167.
MLA	Antonelli, Ray,et al."AS3MT, GSTO, and PNP polymorphisms: Impact on arsenic methylation and implications for disease susceptibility".ENVIRONMENTAL RESEARCH 132(2014):156-167.