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

<h4>Background</h4>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.<h4>Objectives</h4>This study evaluated the interaction between single nucleotide polym...

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Autores principales:	Wen-Chi Pan, Molly L Kile, Wei Jie Seow, Xihong Lin, Quazi Quamruzzaman, Mahmuder Rahman, Golam Mahiuddin, Golam Mostofa, Quan Lu, David C Christiani
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c20896f4d401412292839bcbacae74af
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spelling	oai:doaj.org-article:c20896f4d401412292839bcbacae74af2021-11-18T08:59:44ZGenetic susceptible locus in NOTCH2 interacts with arsenic in drinking water on risk of type 2 diabetes.1932-620310.1371/journal.pone.0070792https://doaj.org/article/c20896f4d401412292839bcbacae74af2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23967108/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Median 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 <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 µg/L showed consistent results for interaction between the NOTCH2 variant and arsenic exposure on T2DM (p for interaction = 0.048; q-value = 0.004).<h4>Conclusions</h4>These 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.Wen-Chi PanMolly L KileWei Jie SeowXihong LinQuazi QuamruzzamanMahmuder RahmanGolam MahiuddinGolam MostofaQuan LuDavid C ChristianiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e70792 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wen-Chi Pan Molly L Kile Wei Jie Seow Xihong Lin Quazi Quamruzzaman Mahmuder Rahman Golam Mahiuddin Golam Mostofa Quan Lu David C Christiani Genetic susceptible locus in NOTCH2 interacts with arsenic in drinking water on risk of type 2 diabetes.
description	<h4>Background</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Median 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 <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 µg/L showed consistent results for interaction between the NOTCH2 variant and arsenic exposure on T2DM (p for interaction = 0.048; q-value = 0.004).<h4>Conclusions</h4>These 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.
format	article
author	Wen-Chi Pan Molly L Kile Wei Jie Seow Xihong Lin Quazi Quamruzzaman Mahmuder Rahman Golam Mahiuddin Golam Mostofa Quan Lu David C Christiani
author_facet	Wen-Chi Pan Molly L Kile Wei Jie Seow Xihong Lin Quazi Quamruzzaman Mahmuder Rahman Golam Mahiuddin Golam Mostofa Quan Lu David C Christiani
author_sort	Wen-Chi Pan
title	Genetic susceptible locus in NOTCH2 interacts with arsenic in drinking water on risk of type 2 diabetes.
title_short	Genetic susceptible locus in NOTCH2 interacts with arsenic in drinking water on risk of type 2 diabetes.
title_full	Genetic susceptible locus in NOTCH2 interacts with arsenic in drinking water on risk of type 2 diabetes.
title_fullStr	Genetic susceptible locus in NOTCH2 interacts with arsenic in drinking water on risk of type 2 diabetes.
title_full_unstemmed	Genetic susceptible locus in NOTCH2 interacts with arsenic in drinking water on risk of type 2 diabetes.
title_sort	genetic susceptible locus in notch2 interacts with arsenic in drinking water on risk of type 2 diabetes.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/c20896f4d401412292839bcbacae74af
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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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