Low-level arsenic exposure, AS3MT gene polymorphism and cardiovascular diseases in rural Texas counties.
ABSTRACT Most Americans living in rural areas use groundwater for drinking. Exposure to low-level (around the current U.S. standard 10 μg/L) arsenic in drinking water is associated with increased mortality of cardiovascular diseases. The current study was to determine if coronary heart disease, hypertension, and hyperlipidemia were associated with low-level arsenic exposure and AS3MT gene single nucleotide polymorphism (SNP) A35991G (rs10748835) in rural Texas. Subjects (156 men, 343 women, 40-96 years of age with a mean of 61) were residents from rural counties Cochran, Palmer, and Bailey, Texas. Groundwater arsenic concentration at each subject's home was estimated with ArcGIS inverse distance weighted interpolation based on the residential location's distances to surrounding wells with known water arsenic concentrations. The estimated groundwater arsenic concentration ranged from 2.2 to 15.3 (mean 6.2) μg/L in this cohort. Logistic regression analysis showed that coronary heart disease was associated with higher arsenic exposure (p<0.05) and with AS3MT genotype GG vs. AA (p<0.05) after adjustments for age, ethnicity, gender, education, smoking status, alcoholism, and anti-hyperlipidemia medication. Hypertension was associated with higher arsenic exposure, while hyperlipidemia was associated with genotype AG vs. AA of the AS3MT gene (p<0.05). Thus, coronary heart disease and its main risk factors were associated with low-level arsenic exposure, AS3MT polymorphism or both.
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ABSTRACT: Oral exposure to inorganic arsenic (iAs) is associated with adverse health effects. Epidemiological studies suggest differences in susceptibility to these health effects, possibly due to genotypic variation. Genetic polymorphisms in iAs metabolism could lead to increased susceptibility by altering urinary iAs metabolite concentrations. To examine the impact of genotypic polymorphisms on iAs metabolism. We screened 360 publications from PubMed and Web of Science for data on urinary mono- and dimethylated arsenic (MMA and DMA) percentages and polymorphic genes encoding proteins that are hypothesized to play roles in arsenic metabolism. The genes we examined were arsenic (+3) methyltransferase (AS3MT), glutathione-s-transferase omega (GSTO), and purine nucleoside phosphorylase (PNP). Relevant data were pooled to determine which polymorphisms are associated across studies with changes in urinary metabolite concentration. In our review, AS3MT polymorphisms rs3740390, rs11191439, and rs11191453 were associated with statistically significant changes in percent urinary MMA. Studies of GSTO polymorphisms did not indicate statistically significant associations with methylation, and there are insufficient data on PNP polymorphisms to evaluate their impact on metabolism. Collectively, these data support the hypothesis that AS3MT polymorphisms alter in vivo metabolite concentrations. Preliminary evidence suggests that AS3MT genetic polymorphisms may impact disease susceptibility. GSTO polymorphisms were not associated with iAs-associated health outcomes. Additional data are needed to evaluate the association between PNP polymorphisms and iAs-associated health outcomes. Delineation of these relationships may inform iAs mode(s) of action and the approach for evaluating low-dose health effects for iAs. Genotype impacts urinary iAs metabolite concentrations and may be a potential mechanism for iAs-related disease susceptibility.Environmental Research 04/2014; 132C:156-167. · 3.24 Impact Factor
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ABSTRACT: The aim was to examine the link between low-level arsenic exposure and cognitive functioning, and the potential role of a single nucleotide polymorphism (SNP A35991G, rs10748835) of the AS3MT gene in modifying this link. Data were analyzed on 526 participants from Project FRONTIER. Hierarchical linear regressions were created with neuropsychological raw index scores as the outcome variable and arsenic exposure and AS3MT SNP as different predictor variables. Within the total sample, arsenic exposure was negatively associated with language (p < 0.001) and executive functioning (p < 0.001). Among those with the AA genotype of the AS3MT gene, arsenic levels were negatively associated with language (p < 0.001), attention (p = 0.01), and executive functioning (p = 0.04). Among those with the AG genotype, arsenic levels were positively associated with immediate (p = 0.04) and delayed memory (p < 0.001) and negatively associated with executive functioning (p = 0.03). Among those with the GG genotype, arsenic levels were negatively associated with visuospatial functioning (p = 0.02). Low-level arsenic exposure is associated with cognitive functioning; however, this association is modified by an AS3MT gene.Environmental Health 03/2014; 13(1):15. · 2.71 Impact Factor
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ABSTRACT: The U.S. Environmental Protection Agency (EPA) is developing an integrated assessment of non-cancer and cancer risk assessment of inorganic arsenic (iAs). Cardiovascular disease (CVD) in association with iAs exposure has been examined in a number of studies and provides a basis for evaluating a reference dose (RfD) for assessing potential non-cancer health risks of arsenic exposure. In this systematic review of low-level iAs exposure (i.e., <100-150μg/L arsenic water concentration) and CVD in human populations, 13 cohort and case-control studies from the United States, Taiwan, Bangladesh, and China were identified and critically examined for evidence for derivation of a RfD. Eight cross-sectional and ecological studies from the United States were also examined for additional information. Prospective cohort data from Bangladesh provided the strongest evidence for determining the point of departure in establishing a candidate RfD based on a combined endpoint of mortality from "ischemic heart disease and other heart diseases." This study as well as the overall literature supported a no-observed-adverse-effect level of 100μg/L for arsenic in water, which was equivalent to an iAs dose of 0.009mg/kg-day (based on population-specific water consumption rates and dietary iAs intake). The study population was likely sensitive to arsenic toxicity because of nutritional deficiencies affecting arsenic methylation and one-carbon metabolism, as well as increasing CVD risk. Evidence is less clear on the interaction of CVD risk factors in the United States (e.g., diabetes, obesity, hypertension) with arsenic at low doses. Potential uncertainty factors up to 3 resulted in a RfD for CVD in the range of 0.003-0.009mg/kg-day. Although caution should be exercised in extrapolating these results to the U.S. general population, these doses allow a margin of exposure that is 10-30 times the current RfD derived by EPA (based on skin lesions in Southwest Taiwan). These findings suggest that the current EPA RfD is protective of CVD.Toxicology 06/2014; · 4.02 Impact Factor