Genetic polymorphisms in MTHFR 677 and 1298, GSTM1 and T1, and metabolism of arsenic

Methylation is the primary route of metabolism of inorganic arsenic in humans, and previous studies showed that interindividual differences in arsenic methylation may have important impacts on susceptibility to arsenic-induced cancer. To date, the factors that regulate arsenic methylation in humans...

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Autores principales: Streinmaus, Craig, Moore, Lee E., Shipp, Miriam, Kalman, Dave, Rey, Omar A., Biggs, Mary Lou, Hopenhayn, Claudia, Bates, Michael N., Zheng, Schichun, Wiencke, John, Smith, Allan H.
Formato: Artículo
Lenguaje:Español
Publicado: 2007
Materias:
R Medicina (General)
Acceso en línea:http://pa.bibdigital.ucc.edu.ar/4043/1/A_Streinmaus.pdf
Aporte de:
Producción Académica Universidad Católica de Córdoba (UCCor) de Universidad Católica de Córdoba
id I38-R144-4043
record_format dspace
spelling I38-R144-40432025-04-14T19:12:56Z http://pa.bibdigital.ucc.edu.ar/4043/ Genetic polymorphisms in MTHFR 677 and 1298, GSTM1 and T1, and metabolism of arsenic Streinmaus, Craig Moore, Lee E. Shipp, Miriam Kalman, Dave Rey, Omar A. Biggs, Mary Lou Hopenhayn, Claudia Bates, Michael N. Zheng, Schichun Wiencke, John Smith, Allan H. R Medicina (General) Methylation is the primary route of metabolism of inorganic arsenic in humans, and previous studies showed that interindividual differences in arsenic methylation may have important impacts on susceptibility to arsenic-induced cancer. To date, the factors that regulate arsenic methylation in humans are mostly unknown. Urinary arsenic methylation patterns and genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and glutathione S-transferase (GST) were investigated in 170 subjects from an arsenic-exposed region in Argentina. Previous studies showed that subjects with the TT/AA polymorphisms at MTHFR 677 and 1298 have lower MTHFR activity than others. In this study, it was found that subjects with the TT/AA variant of MTHFR 677/1298 excreted a significantly higher proportion of ingested arsenic as inorganic arsenic and a lower proportion as dimethylarsinic acid. Women with the null genotype of GSTM1 excreted a significantly higher proportion of arsenic as monomethylarsonate than women with the active genotype. No associations were seen between polymorphisms in GSTT1 and arsenic methylation. This is the first study to report (1) associations between MTHFR and arsenic metabolism in humans, and (2) gender differences between genetic polymorphisms and urinary arsenic methylation patterns. Overall, this study provides evidence that MTHFR and GSTM1 are involved in arsenic metabolism in humans, and polymorphisms in the genes that encode these enzymes may play a role in susceptibility to arsenic-induced cancer. 2007-01-01 info:eu-repo/semantics/article info:eu-repo/semantics/closedAccess application/pdf spa http://pa.bibdigital.ucc.edu.ar/4043/1/A_Streinmaus.pdf Streinmaus, Craig, Moore, Lee E., Shipp, Miriam, Kalman, Dave, Rey, Omar A. ORCID: https://orcid.org/0000-0002-9232-1252 <https://orcid.org/0000-0002-9232-1252>, Biggs, Mary Lou, Hopenhayn, Claudia, Bates, Michael N., Zheng, Schichun, Wiencke, John ORCID: https://orcid.org/0000-0001-7101-6489 <https://orcid.org/0000-0001-7101-6489> and Smith, Allan H. (2007) Genetic polymorphisms in MTHFR 677 and 1298, GSTM1 and T1, and metabolism of arsenic. Journal of Toxicology and Environmental Health - Part A: Current Issues, 70 (2). pp. 159-170. ISSN 1087-2620 info:eu-repo/semantics/altIdentifier/doi/10.1080/15287390600755240
institution Universidad Católica de Córdoba
institution_str I-38
repository_str R-144
collection Producción Académica Universidad Católica de Córdoba (UCCor)
language Español
orig_language_str_mv spa
topic R Medicina (General)
spellingShingle R Medicina (General)
Streinmaus, Craig
Moore, Lee E.
Shipp, Miriam
Kalman, Dave
Rey, Omar A.
Biggs, Mary Lou
Hopenhayn, Claudia
Bates, Michael N.
Zheng, Schichun
Wiencke, John
Smith, Allan H.
Genetic polymorphisms in MTHFR 677 and 1298, GSTM1 and T1, and metabolism of arsenic
topic_facet R Medicina (General)
description Methylation is the primary route of metabolism of inorganic arsenic in humans, and previous studies showed that interindividual differences in arsenic methylation may have important impacts on susceptibility to arsenic-induced cancer. To date, the factors that regulate arsenic methylation in humans are mostly unknown. Urinary arsenic methylation patterns and genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and glutathione S-transferase (GST) were investigated in 170 subjects from an arsenic-exposed region in Argentina. Previous studies showed that subjects with the TT/AA polymorphisms at MTHFR 677 and 1298 have lower MTHFR activity than others. In this study, it was found that subjects with the TT/AA variant of MTHFR 677/1298 excreted a significantly higher proportion of ingested arsenic as inorganic arsenic and a lower proportion as dimethylarsinic acid. Women with the null genotype of GSTM1 excreted a significantly higher proportion of arsenic as monomethylarsonate than women with the active genotype. No associations were seen between polymorphisms in GSTT1 and arsenic methylation. This is the first study to report (1) associations between MTHFR and arsenic metabolism in humans, and (2) gender differences between genetic polymorphisms and urinary arsenic methylation patterns. Overall, this study provides evidence that MTHFR and GSTM1 are involved in arsenic metabolism in humans, and polymorphisms in the genes that encode these enzymes may play a role in susceptibility to arsenic-induced cancer.
format Artículo
author Streinmaus, Craig
Moore, Lee E.
Shipp, Miriam
Kalman, Dave
Rey, Omar A.
Biggs, Mary Lou
Hopenhayn, Claudia
Bates, Michael N.
Zheng, Schichun
Wiencke, John
Smith, Allan H.
author_facet Streinmaus, Craig
Moore, Lee E.
Shipp, Miriam
Kalman, Dave
Rey, Omar A.
Biggs, Mary Lou
Hopenhayn, Claudia
Bates, Michael N.
Zheng, Schichun
Wiencke, John
Smith, Allan H.
author_sort Streinmaus, Craig
title Genetic polymorphisms in MTHFR 677 and 1298, GSTM1 and T1, and metabolism of arsenic
title_short Genetic polymorphisms in MTHFR 677 and 1298, GSTM1 and T1, and metabolism of arsenic
title_full Genetic polymorphisms in MTHFR 677 and 1298, GSTM1 and T1, and metabolism of arsenic
title_fullStr Genetic polymorphisms in MTHFR 677 and 1298, GSTM1 and T1, and metabolism of arsenic
title_full_unstemmed Genetic polymorphisms in MTHFR 677 and 1298, GSTM1 and T1, and metabolism of arsenic
title_sort genetic polymorphisms in mthfr 677 and 1298, gstm1 and t1, and metabolism of arsenic
publishDate 2007
url http://pa.bibdigital.ucc.edu.ar/4043/1/A_Streinmaus.pdf
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