A large-scale genomic study conducted in Bangladesh has discovered genetic variants that control arsenic metabolism and elevate the risk of skin lesions in people chronically exposed to arsenic. In PLoS Genetics, researchers from the University of Chicago, Columbia University, the International Center for Diarrheal Disease Research in Bangladesh, and the University of North Carolina report that genetic variants found near the enzyme for metabolizing the chemical into a less toxic form are associated with an individual's risk of developing arsenic-related disease.
Since the installation of hand-pumped wells to tap groundwater sources in the 1970s, as many as 77 million people – about half the population of Bangladesh – have been accidentally exposed to dangerous levels of arsenic. The World Health Organization calls the exposure "the largest mass poisoning of a population in history" (WHO, 2000).
For over a decade, Habibul Ahsan and colleagues have studied the epidemiology of arsenic-related diseases such as skin lesions, diabetes, and cardiovascular and respiratory illnesses in this population, as well as the effectiveness of interventions to prevent toxicity. In this new study, nearly 3,000 Bangladeshis were genotyped for variants throughout the genome, in a search for answers as to why some individuals appear to be at higher risk for developing disease after arsenic exposure.
The research team found genetic variants associated with arsenic metabolite levels and skin lesion risk in the region of a likely candidate gene: arsenite methyltransferase, an enzyme critical for arsenic metabolism. A study of gene expression levels found that those same variants were associated with reduced expression of the enzyme. Boosting arsenic metabolism may be an effective intervention in individuals exposed to the toxin and at high genetic risk from arsenic-related disease.
"These results add clarity to the genetic architecture that is playing a role in the arsenic toxicity and its underlying biological basis," said Ahsan. "It's an important study for a major problem affecting millions of people around the world, and it opens up opportunities for genetic studies of other major public health problems in developing countries."
FINANCIAL DISCLOSURE: This work was supported by NIH Grants P42ES010349, R01CA102484, R01CA107431, and P30CA014599 and by Department of Defense grant W81XWH-10-1-0499. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
COMPETING INTERESTS: The authors have declared that no competing interests exist.
CITATION: Pierce BL, Kibriya MG, Tong L, Jasmine F, Argos M, et al. (2012) Genome-Wide Association Study Identifies Chromosome 10q24.32 Variants Associated with Arsenic Metabolism and Toxicity Phenotypes in Bangladesh. PLoS Genet 8(2): e1002522. doi:10.1371/journal.pgen.1002522
CONTACT:
Habibul Ahsan
University of Chicago
Health Studies, Medicine and Human Genetics and Cancer Research
AMB N102A (MC 2007)
5841 South Maryland Avenue,
Chicago, Illinois 60637
UNITED STATES
PHONE: 773-834-9956
FAX: 773-834-0139
EMAIL: habib@uchicago.edu
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