Arsenic Methylation, GSTT1, GSTM1, GSTP1 Polymorphisms, and Skin Lesions Kathleen M. McCarty,1,2 Yen-Ching Chen,2 Quazi Quamruzzaman,3 Mahmuder Rahman,3 Golam Mahiuddin,3 Yu-Mei Hsueh,4 Li Su,2 Thomas Smith,2 Louise Ryan,5 and David C. Christiani2 1Yale University School of Medicine, Epidemiology and Public Health, Division of Environmental Health Sciences, New Haven, Connecticut, USA; 2Harvard School of Public Health, Department of Environmental Health, Boston, Massachusetts, USA; 3Dhaka Community Hospital, Dhaka, Bangladesh; 4School of Medicine, Department of Public Health, Taipei Medical College, Taipei, Taiwan; 5Harvard School of Public Health, Department of Biostatistics, Boston, Massachusetts, USA 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 wildtypeand 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 methylation 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 wildtypeand secondary methylation ratio modifies risk of skin lesions among arsenic-exposed individuals. Key words: arsenic methylation, DMA, GSTpolymorphisms, methylation ratio, MMA, primary methylation, secondary methylation. Environ Health Perspect 115:341–345 (2007) . doi:10.1289/ehp.9152 available via http://dx.doi.org/ [Online 20 December 2006] Address correspondence to K.M. McCarty, Yale University School of Medicine Epidemiology and Public Health, Division of Environmental Health Sciences, 60 College St., LEPH 442, New Haven, CT 06520 USA. Telephone: (203) 785-6063. Fax: (203) 737-6023. Kathleen.McCarty@yale.edu We gratefully acknowledge A. Smith, R. Wilson, and H. Ahsan for their expertise ; the Dhaka Community Hospital field team for subject recruitment, sample collection, and data entry ; J. Frelich for data management and L. Portier for programming assistance ; Z. Wei, M. Wang, and T. Van Geel in the Harvard Molecular Epidemiology Laboratory ; and L. Shimada for her expertise and assistance in human subjects approval. This work was supported by grants ES 05947, ES 00002, and ES 11622 from the National Institutes of Health (NIH) . K.M.M. was supported by training grant T32ES 06790 from the National Institute of Environmental Health Sciences, NIH. The authors declare they have no competing financial interests. Received 8 March 2006 ; accepted 20 December 2006. The full version of this article is available for free in HTML or PDF formats. |