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

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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., Christiani, D. C., Kile, M. L., Seow, W. J., Lin, X., Quamruzzaman, Q., . . . Lu, Q. (2013). Genetic susceptible locus in NOTCH2 interacts with arsenic in drinking water on risk of type 2 diabetes. PloS One, 8(8), e70792.
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  • description.provenance : Approved for entry into archive by Deborah Campbell(deborah.campbell@oregonstate.edu) on 2013-09-19T15:43:30Z (GMT) No. of bitstreams: 2 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) KileMollyLPublicHealthHumanScienceGeneticSusceptibleLocus.pdf: 206701 bytes, checksum: 0be3c0f732b189f2983f9dd8bec59b05 (MD5)
  • description.provenance : Made available in DSpace on 2013-09-19T15:43:30Z (GMT). No. of bitstreams: 2 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) KileMollyLPublicHealthHumanScienceGeneticSusceptibleLocus.pdf: 206701 bytes, checksum: 0be3c0f732b189f2983f9dd8bec59b05 (MD5) Previous issue date: 2013-08-14
  • description.provenance : Submitted by Deborah Campbell (deborah.campbell@oregonstate.edu) on 2013-09-19T15:41:39Z No. of bitstreams: 2 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) KileMollyLPublicHealthHumanScienceGeneticSusceptibleLocus.pdf: 206701 bytes, checksum: 0be3c0f732b189f2983f9dd8bec59b05 (MD5)

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