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Genetic Susceptible Locus in NOTCH2 Interacts with Arsenic in Drinking Water on Risk of Type 2 Diabetes

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https://ir.library.oregonstate.edu/concern/articles/bn999744w

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  • Abstract: Background: Chronic exposure to arsenic in drinking water is associated with increased risk of type 2 diabetes mellitus (T2DM) but the underlying molecular mechanism remains unclear. Objectives: This study evaluated the interaction between single nucleotide polymorphisms (SNPs) in genes associated with diabetes and arsenic exposure in drinking water on the risk of developing T2DM. Methods: In 2009-2011, we conducted a follow up study of 957 Bangladeshi adults who participated in a case-control study of arsenic-induced skin lesions in 2001-2003. Logistic regression models were used to evaluate the association between 38 SNPs in 18 genes and risk of T2DM measured at follow up. T2DM was defined as having a blood hemoglobin A1C level greater than or equal to 6.5% at follow-up. Arsenic exposure was characterized by drinking water samples collected from participants' tubewells. False discovery rates were applied in the analysis to control for multiple comparisons. Results: Median arsenic levels in 2001-2003 were higher among diabetic participants compared with non-diabetic ones (71.6 mu g/L vs. 12.5 mu g/L, p-value <0.001). Three SNPs in ADAMTS9 were nominally associated with increased risk of T2DM (rs17070905, Odds Ratio (OR) = 2.30, 95% confidence interval (CI) 1.17-4.50; rs17070967, OR = 2.02, 95% CI 1.00-4.06; rs6766801, OR = 2.33, 95% CI 1.18-4.60), but these associations did not reach the statistical significance after adjusting for multiple comparisons. A significant interaction between arsenic and NOTCH2 (rs699780) was observed which significantly increased the risk of T2DM (p for interaction = 0.003; q-value = 0.021). Further restricted analysis among participants exposed to water arsenic of less than 148 mu g/L showed consistent results for interaction between the NOTCH2 variant and arsenic exposure on T2DM (p for interaction = 0.048; q-value = 0.004).
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  • Pan W-C, Kile ML, Seow WJ, Lin X, Quamruzzaman Q, Rahman M, et al. (2013) Genetic Susceptible Locus in NOTCH2 Interacts with Arsenic in Drinking Water on Risk of Type 2 Diabetes. PLoS ONE 8(8): e70792. https://doi.org/10.1371/journal.pone.0070792
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  • 8
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  • 8
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  • This work was supported by the Harvard School of Public Health (Gene and Environment Initiative grant) and U.S.A. National Institute of Environmental Health Sciences (P42ES016454, K01ES017800, RO1ES011622, R01ES022230, and P30ES000002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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