Dataset Information

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

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 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).

Conclusions

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.

SUBMITTER: Pan WC

PROVIDER: S-EPMC3743824 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Pan Wen-Chi WC Kile Molly L ML Seow Wei Jie WJ Lin Xihong X Quamruzzaman Quazi Q Rahman Mahmuder M Mahiuddin Golam G Mostofa Golam G Lu Quan Q Christiani David C DC

PloS one 20130814 8

<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 ...[more]

PMID: 23967108

Similar Datasets

Project description:Arsenic contamination of drinking water is a serious public health threat. In Bangladesh, eight major safe water options provide an alternative to contaminated shallow tubewells: piped water supply, deep tubewells, pond sand filters, community arsenic-removal, household arsenic removal, dug wells, well-sharing, and rainwater harvesting. However, it is uncertain how well these options are accepted and used by the at-risk population. Based on the RANAS model (risk, attitudes, norms, ability, and self-regulation) this study aimed to identify the acceptance and use of available safe water options. Cross-sectional face-to-face interviews were used to survey 1,268 households in Bangladesh in November 2009 (n = 872), and December 2010 (n = 396). The questionnaire assessed water consumption, acceptance factors from the RANAS model, and socioeconomic factors. Although all respondents had access to at least one arsenic-safe drinking water option, only 62.1% of participants were currently using these alternatives. The most regularly used options were household arsenic removal filters (92.9%) and piped water supply (85.6%). However, the former result may be positively biased due to high refusal rates of household filter owners. The least used option was household rainwater harvesting (36.6%). Those who reported not using an arsenic-safe source differed in terms of numerous acceptance factors from those who reported using arsenic-safe sources: non-users were characterized by greater vulnerability; showed less preference for the taste and temperature of alternative sources; found collecting safe water quite time-consuming; had lower levels of social norms, self-efficacy, and coping planning; and demonstrated lower levels of commitment to collecting safe water. Acceptance was particularly high for piped water supplies and deep tubewells, whereas dug wells and well-sharing were the least accepted sources. Intervention strategies were derived from the results in order to increase the acceptance and use of each arsenic-safe water option.

Project description:Evidence-based public health policy often comes years or decades after the underlying scientific breakthrough. The World Health Organization's (WHO's) provisional 10 μg/L arsenic (As) drinking water guideline was set in 1993 based on "analytical achievability." In 2011, an additional proviso of "treatment performance" was added; a health-based risk assessment would lead to a lower and more protective guideline. Since the WHO does not require United Nations member states to submit copies of national drinking water regulations, there is no complete database of national drinking water standards or guidelines. In this study, we collated and analyzed all drinking water regulations for As from national governments worldwide. We found regulations for 176 countries. Of these countries, 136 have drinking water regulations that specify 10 μg/L As or less, while 40 have regulations that allow more than 10 μg/L of As; we could not find any evidence of regulations for 19 countries. The number of people living in countries that do not meet the WHO's guideline constitutes 32% of the global population. Global As regulations are also strongly tied to national income, with high income countries more likely to meet the WHO's guideline. In this study, we examined the health risk assessments that show a clear need for reducing As exposure to levels far below the current WHO provisional guideline. We also show that advances in analytical chemistry, drinking water treatment, and the possibility of accessing alternative drinking water supplies without As suggest that both low-income countries with limited resources and high-income countries with adequate resources can adopt a lower and more protective national drinking water standards or guidelines for As. Thus, we recommend that regulators and stake holders of all nations reassess the possibilities for improving public health and reducing health care expenses by adopting more stringent regulations for As in drinking water.

Dataset Information

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

Background

Objectives

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets