Document Detail


Polymorphisms in the human monomethylarsonic acid (MMA V) reductase/hGSTO1 gene and changes in urinary arsenic profiles.
MedLine Citation:
PMID:  14680363     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Large interindividual variability in urinary arsenic profiles, following chronic inorganic arsenic exposure, is well-known in humans. To understand this variability, we studied the relationship between polymorphisms in the gene for human monomethylarsonic acid (MMA(V)) reductase/hGSTO1 and the urinary arsenic profiles of individuals chronically exposed to arsenic in their drinking water. To ensure that we did not overlook rare polymorphisms, not included in the public databases, we amplified and sequenced all six exons of the gene and their flanking regions, using DNA isolated from peripheral blood samples of 75 subjects, living in the vicinity of Torreon, Mexico. Four groups, based on the levels of arsenic (9-100 microg/L) in their drinking water, were studied. We identified six novel polymorphisms and two reported previously. The novel polymorphisms were a three base pair deletion (delGGC) in the first intron; a G > C transversion, leading to a serine-to-cysteine substitution at amino acid 86; a G > T transversion and a A > T transversion in intron 5; a G > A transition resulting in glutamate-to-lysine substitution in amino acid 208; and a C > T transition producing an alanine-to-valine substitution in amino acid 236. Two subjects displayed significant differences in patterns of urinary arsenic; they had increased levels of urinary inorganic arsenic and reduced levels of methylated urinary arsenic species as compared to the rest of the study population. These two subjects had the same unique polymorphisms in hGSTO1 in that they were heterozygous for E155del and Glu208Lys. The identified SNPs may be one of the reasons for the large interindividual variability in the response of humans to chronic inorganic arsenic exposure. The findings suggest the need for further studies to identify unambiguously specific polymorphisms that may account for interindividual variability in the human response to chronic inorganic arsenic exposure.
Authors:
Lorraine L Marnell; Gonzalo G Garcia-Vargas; Uttam K Chowdhury; Robert A Zakharyan; Bruce Walsh; Mihaela D Avram; Michael J Kopplin; Mariano E Cebrián; Ellen K Silbergeld; H Vasken Aposhian
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Chemical research in toxicology     Volume:  16     ISSN:  0893-228X     ISO Abbreviation:  Chem. Res. Toxicol.     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2003-12-18     Completed Date:  2004-04-29     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8807448     Medline TA:  Chem Res Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1507-13     Citation Subset:  IM    
Affiliation:
Department of Molecular and Cellular Biology, Center for Toxicology, University of Arizona, Tucson Arizona 85721-0106, USA.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Arsenic / chemistry,  urine*
Arsenicals / metabolism*
Chromosome Mapping
DNA Primers / genetics
Exons / genetics
Female
Genotype
Glutathione Transferase / genetics*,  metabolism
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide / genetics
Grant Support
ID/Acronym/Agency:
ES-04940/ES/NIEHS NIH HHS; P30-ES-06694/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Arsenicals; 0/DNA Primers; 124-58-3/monomethylarsonic acid; 7440-38-2/Arsenic; EC 2.5.1.18/Glutathione Transferase

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