Skip to main content
Log in

Genetic variants associated with arsenic metabolism within human arsenic (+3 oxidation state) methyltransferase show wide variation across multiple populations

  • Regulatory Toxicology
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Human arsenic (+3 oxidation state) methyltransferase (AS3MT) is known to catalyze the methylation of arsenite. The objective of this study was to investigate the diversity of the AS3MT gene in Mexican and German populations. The distribution of 18 single nucleotide polymorphisms (SNPs) in AS3MT was assessed on healthy individuals: 38 Mestizo, 69 Nahuas, 50 Huicholes, and 32 Germans. All 18 SNPs were polymorphic in the German and Mexican populations. Of the three Mexican populations, a minor allele frequency was the highest in the Mestizo, followed by the Nahuas and Huicholes. In the German and three Mexican groups, haplotype #1(TATAGAAGTCTTCATGAC) was the most predominant. Seven haplotypes were newly found in the German and three Mexican populations. The D′ values between SNP pairs were high in the German and Nahua populations; they had a similar pattern. The pattern of the Mestizo was more similar to the African than to the other Mexican populations. Huicholes had a moderate pattern of the African and German/Nahua populations. The network had three clusters. One originated in the African population and another may have originated in an Asian (Chinese and/or Japanese) population. The third one may have originated among Caucasians. This study is the first to demonstrate the existence of genetic heterogeneity in the distribution of 18 SNPs in AS3MT of German and Mexican populations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • ATSDR (2006) Arsenic. Chemical agent briefing sheet. Available: http://www.atsdr.cdc.gov/cabs/arsenic/index.html#effect

  • Cebrián ME et al (1994) Chronic arsenic poisoning in humans. The case of Mexico. In: Niriagu JO (ed) Arsenic in the environment. part II: human health and ecosystem effects. Wiley, New York, pp 93–107

    Google Scholar 

  • Fujihara J, Kunito T, Agusa T, Yasuda T, Iida R, Takeshita H (2007a) Population differences in the human arsenic methyltransferase (AS3MT) gene polymorphism detected by using genotyping method. Toxicol Appl Pharmacol 225:251–254

    Article  CAS  PubMed  Google Scholar 

  • Fujihara J, kunito T, Takeshita H (2007b) Frequency of two human glutathione-S-transferase omega 1 polymorphisms (E155 deletion and E208 K) in Ovambo and Japanese populations using the PCR-based genotyping method. Clin Chem Lab Med 45:621–624

    Article  CAS  PubMed  Google Scholar 

  • Fujihara J, Fujii Y, Agusa T, Kunito T, Yasuda T, Takeshita H (2009) Ethnic differences in five intronic polymorphisms associated with arsenic metabolism within human arsenic (+3 oxidation state) methyltransferase (AS3MT) gene. Toxicol Appl Pharmacol 234:41–46

    Article  CAS  PubMed  Google Scholar 

  • Fujihara J, Fujii Y, Agusa T, Kunito T, Yasuda T, Takeshita H (2010) Global analysis of genetic variation in human arsenic (+3 oxidation state) methyltransferase (AS3MT). Toxicol Appl Pharmacol 243:292–299

    Article  CAS  PubMed  Google Scholar 

  • Hernández A, Xamena N, Surrallés J, Sekaran C, Tokunaga H, Quinteros D, Amadeu Creus A, Marcos R (2008a) Role of the Met 287 Thr polymorphism in the AS3MT gene on the metabolic arsenic profile. Mutat Res 637:80–92

    PubMed  Google Scholar 

  • Hernández A, Xamena N, Sekaran C, Tokunaga H, Sampayo-Reyes A, Quinteros D, Amadeu Creus A, Marcos R (2008b) High arsenic metabolic efficiency in AS3MT287Thr allele carriers. Pharmacogenet Genomics 18:349–355

    Article  PubMed  Google Scholar 

  • IARC (1980) Some metals and metallic compounds. IARC monographs on the evaluation of the carcinogenic risk to humans, vol. 23. IARC, Lyon, France, pp 39–141

    Google Scholar 

  • Lin S, Shi Q, Nix FB, Styblo M, Beck MA, Herbin-Davis KM, Hall LL, Simeonsson JB, Thomas DJ (2002) A novel S-adenosyl-L-methionine: arsenic (III) methyltransferase from rat liver cytosol. J Biol Chem 277:10795–10803

    Article  CAS  PubMed  Google Scholar 

  • 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. Environ Health Perspect 115:1081–1086

    Article  CAS  PubMed  Google Scholar 

  • Marnell LL, Garcia-Vargas GG, Chowdhury UK, Zakharyan RA, Walsh B, Avram MD (2003) Polymorphism in the human monomethylarsonic acid (mmav) reductase/hgsto1 gene and changes in urinary arsenic profiles. Chem Res Toxicol 16:1507–1513

    Article  CAS  PubMed  Google Scholar 

  • Meza MM, Yu L, Rodriguez YY, Guild M, Thompson D, Gandolfi AJ, Klimecki WT (2005) Developmentally restricted genetic determinants of human arsenic metabolism: association between urinary methylated arsenic and CYT19 polymorphism in children. Environ Health Perspect 113:775–781

    Article  CAS  PubMed  Google Scholar 

  • Meza MM, Gandolfi AJ, Klimecki WT (2007) Developmental and genetic modulation of arsenic biotransformation: A gene by environmental interaction. Toxicol Appl Pharmacol 222:381–387

    Article  CAS  PubMed  Google Scholar 

  • Navas-Acien A, Silbergeld EK, Pastor-Barriuso R, Guallar E (2008) Arsenic exposure and prevalence of type 2 diabetes in US adults. JAMA 300:814–822

    Article  CAS  PubMed  Google Scholar 

  • NRC (1999) Arsenic in drinking water. National academy press, Washington, DC

    Google Scholar 

  • Rossman TG (2003) Mechanism of arsenic carcinogenesis: an integrated approach. Mutat Res 533:37–65

    CAS  PubMed  Google Scholar 

  • Schläwicke Engström KS, Broberg K, Concha G, Nermell B, Warholm M (2007) Genetic polymorphisms influencing arsenic metabolism: evidence from Argentina. Environ Health Perspect 115:599–605

    Article  PubMed  Google Scholar 

  • Stephens M, Donelly PA (2003) Comparison of bayesian methods for haplotype reconstruction from population genotype data. Am J Hum Genet 273:1162–1169

    Article  Google Scholar 

  • Vahter M (2000) Genetic polymorphism in the biotransformation of inorganic and its role in toxicity. Toxicol Lett 112–113:209–217

    Article  PubMed  Google Scholar 

  • Vahter M (2002) Mechanisms of arsenic biotransformation. Toxicology 181–182:211–217

    Article  PubMed  Google Scholar 

  • Valenzuela OL, Drobná Z, Hernández-Castellanos E, Sánchez-Peña LC, García-Vargas GG, Borja-Aburto VH, Stýblo M, Del Razo LM (2009) Association of AS3MT polymorphisms and the risk of premalignant arsenic skin lesions. Toxicol Appl Pharmacol 239:200–207

    Article  CAS  PubMed  Google Scholar 

  • Whitbread AK, Tetlow N, Eyre HJ, Sutherland GR, Board PG (2003) Characterization of the human omega class glutathione transferase genes and associated polymorphisms. Pharmacogenetics 13:131–144

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was partially supported by Grants-in-Aid from the Japan Society for the Promotion of Science (19209025 and 21659175 to H. Takeshita and 21590736 to J. Fujihara).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Haruo Takeshita.

Electronic supplementary material

Below is the link to the electronic supplementary material.

(XLS 31 kb)

(XLS 32 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fujihara, J., Yasuda, T., Kato, H. et al. Genetic variants associated with arsenic metabolism within human arsenic (+3 oxidation state) methyltransferase show wide variation across multiple populations. Arch Toxicol 85, 119–125 (2011). https://doi.org/10.1007/s00204-010-0568-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-010-0568-y

Keywords

Navigation