PLoS ONE (Jan 2013)

Genetic susceptible locus in NOTCH2 interacts with arsenic in drinking water on risk of type 2 diabetes.

  • Wen-Chi Pan,
  • Molly L Kile,
  • Wei Jie Seow,
  • Xihong Lin,
  • Quazi Quamruzzaman,
  • Mahmuder Rahman,
  • Golam Mahiuddin,
  • Golam Mostofa,
  • Quan Lu,
  • David C Christiani

DOI
https://doi.org/10.1371/journal.pone.0070792
Journal volume & issue
Vol. 8, no. 8
p. e70792

Abstract

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BackgroundChronic exposure to arsenic in drinking water is associated with increased risk of type 2 diabetes mellitus (T2DM) but the underlying molecular mechanism remains unclear.ObjectivesThis 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.MethodsIn 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.ResultsMedian arsenic levels in 2001-2003 were higher among diabetic participants compared with non-diabetic ones (71.6 µg/L vs. 12.5 µg/L, p-value ConclusionsThese findings suggest that genetic variation in NOTCH2 increased susceptibility to T2DM among people exposed to inorganic arsenic. Additionally, genetic variants in ADAMTS9 may increase the risk of T2DM.