Metabolism of low-dose inorganic arsenic in a central European population

Influence of sex and genetic polymorphisms

Anna Lena Lindberg, Rajiv Kumar, Walter Goessler, Ranjit Thirumaran, Eugen Gurzau, Kvetoslava Koppova, P. Rudnai, Giovanni Leonardi, Tony Fletcher, Marie Vahter

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

Background: There is a wide variation in susceptibility to health effects of arsenic, which, in part, may be due to differences in arsenic metabolism. Arsenic is metabolized by reduction and methylation reactions, catalyzed by reductases and methyltransferases. Objectives: Our goal in this study was to elucidate the influence of various demographic and genetic factors on the metabolism of arsenic. Methods: We studied 415 individuals from Hungary, Romania, and Slovakia by measuring arsenic metabolites in urine using liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry (HPLC-HG-ICPMS). We performed genotyping of arsenic (+III) methyltransferase (AS3MT), glutathione S-transferase omega 1 (GSTO1), and methylene-tetrahydrofolate reductase (MTHFR). Results: The results show that the M287T (T→C) polymorphism in the AS3MT gene, the A222V (C→T) polymorphism in the MTHFR gene, body mass index, and sex are major factors that influence arsenic metabolism in this population, with a median of 8.0 μg/L arsenic in urine. Females <60 years of age had, in general, higher methylation efficiency than males, indicating an influence of sex steroids. That might also explain the observed better methylation in overweight or obese women, compared with normal weight men. The influence of the M287T (T→C) polymorphism in the AS3MT gene on the methylation capacity was much more pronounced in men than in women. Conclusions: The factors investigated explained almost 20% of the variation seen in the metabolism of arsenic among men and only around 4% of the variation among women. The rest of the variation is probably explained by other methyltransferases backing up the methylation of arsenic.

Original languageEnglish
Pages (from-to)1081-1086
Number of pages6
JournalEnvironmental Health Perspectives
Volume115
Issue number7
DOIs
Publication statusPublished - Jul 2007

Fingerprint

Arsenic
Genetic Polymorphisms
Polymorphism
Metabolism
arsenic
polymorphism
metabolism
Methylation
methylation
Population
Methyltransferases
Methylenetetrahydrofolate Reductase (NADPH2)
Genes
urine
gene
dose
Urine
Sex Factors
Inductively coupled plasma mass spectrometry
Romania

Keywords

  • Arsenic
  • AS4MT
  • Blood
  • GSTO1
  • Methylation
  • MTHFR
  • Polymorphisms
  • Sex
  • Urine

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Public Health, Environmental and Occupational Health

Cite this

Lindberg, A. L., Kumar, R., Goessler, W., Thirumaran, R., Gurzau, E., Koppova, K., ... Vahter, M. (2007). Metabolism of low-dose inorganic arsenic in a central European population: Influence of sex and genetic polymorphisms. Environmental Health Perspectives, 115(7), 1081-1086. https://doi.org/10.1289/ehp.10026

Metabolism of low-dose inorganic arsenic in a central European population : Influence of sex and genetic polymorphisms. / Lindberg, Anna Lena; Kumar, Rajiv; Goessler, Walter; Thirumaran, Ranjit; Gurzau, Eugen; Koppova, Kvetoslava; Rudnai, P.; Leonardi, Giovanni; Fletcher, Tony; Vahter, Marie.

In: Environmental Health Perspectives, Vol. 115, No. 7, 07.2007, p. 1081-1086.

Research output: Contribution to journalArticle

Lindberg, AL, Kumar, R, Goessler, W, Thirumaran, R, Gurzau, E, Koppova, K, Rudnai, P, Leonardi, G, Fletcher, T & Vahter, M 2007, 'Metabolism of low-dose inorganic arsenic in a central European population: Influence of sex and genetic polymorphisms', Environmental Health Perspectives, vol. 115, no. 7, pp. 1081-1086. https://doi.org/10.1289/ehp.10026
Lindberg, Anna Lena ; Kumar, Rajiv ; Goessler, Walter ; Thirumaran, Ranjit ; Gurzau, Eugen ; Koppova, Kvetoslava ; Rudnai, P. ; Leonardi, Giovanni ; Fletcher, Tony ; Vahter, Marie. / Metabolism of low-dose inorganic arsenic in a central European population : Influence of sex and genetic polymorphisms. In: Environmental Health Perspectives. 2007 ; Vol. 115, No. 7. pp. 1081-1086.
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