Arsenic methylation, GSTT1, GSTM1, GSTP1 polymorphisms, and skin lesions

Kathleen M. McCarty, Yen Ching Chen, Quazi Quamruzzaman, Mahmuder Rahman, Golam Mahiuddin, Yu Mei Hsueh, Li Su, Thomas Smith, Louise Ryan, David C. Christiani

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Abstract

Objective: We investigated whether primary and secondary arsenic methylation ratios were associated with skin lesions and whether GSTT1, GSTP1, and GSTM1 polymorphisms modify these relationships. Methods: A case-control study of 600 cases and 600 controls that were frequency matched on age and sex was conducted in Pabna, Bangladesh, in 2001-2002. Individual well water, urine, and blood samples were collected. Water arsenic concentration was determined using inductively coupled plasma mass spectrometry (ICP-MS). Urinary arsenic speciation was determined using high performance liquid chromatography hydride with generator atomic absorption spectrometry and ICP-MS. Genotyping was conducted using multiplex polymerase chain reaction and TaqMan. Results: A 10-fold increase in primary methylation ratio [monomethylarsonic acid (MMA)/(arsenite + arsenate) was associated with a 1.50-fold increased risk of skin lesions (multivariate odds ratio = 1.50; 95% confidence interval, 1.00-2.26). We observed significant interaction on the multiplicative scale between GSTT1 wildtype and secondary methylation ratio [dimethylarsinic acid/MMA; likelihood ratio test (LRT), p = 0.01]. No significant interactions were observed for GSTM1 or GSTP1 or for primary mathylation ratios. Conclusion: Our findings suggest that increasing primary methylation ratios are associated with an increase in risk of arsenic-related skin lesions. The interaction between GSTT1 wildtype and secondary methylation ratio modifies risk of skin lesions among arsenic-exposed individuals.

Original languageEnglish
Pages (from-to)341-345
Number of pages5
JournalEnvironmental Health Perspectives
Volume115
Issue number3
DOIs
Publication statusPublished - Mar 2007

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Keywords

  • Arsenic methylation
  • DMA
  • GST polymorphisms
  • Methylation ratio
  • MMA
  • Primary methylation
  • Secondary methylation

ASJC Scopus subject areas

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

Cite this

McCarty, K. M., Chen, Y. C., Quamruzzaman, Q., Rahman, M., Mahiuddin, G., Hsueh, Y. M., Su, L., Smith, T., Ryan, L., & Christiani, D. C. (2007). Arsenic methylation, GSTT1, GSTM1, GSTP1 polymorphisms, and skin lesions. Environmental Health Perspectives, 115(3), 341-345. https://doi.org/10.1289/ehp.9152