Association of AS3MT polymorphisms and the risk of premalignant arsenic skin lesions.

Exposure to naturally occurring inorganic arsenic (iAs), primarily from contaminated drinking water, is considered one of the top environmental health threats worldwide. Arsenic (+3 oxidation state) methyltransferase (AS3MT) is the key enzyme in the biotransformation pathway of iAs. AS3MT catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to trivalent arsenicals, resulting in the production of methylated (MAs) and dimethylated arsenicals (DMAs). MAs is a susceptibility factor for iAs-induced toxicity. In this study, we evaluated the association of the polymorphism in AS3MT gene with iAs metabolism and with the presence of arsenic (As) premalignant skin lesions. This is a case-control study of 71 cases with skin lesions and 51 controls without skin lesions recruited from a iAs endemic area in Mexico. We measured urinary As metabolites, differentiating the trivalent and pentavalent arsenical species, using the hydride generation atomic absorption spectrometry. In addition, the study subjects were genotyped to analyze three single nucleotide polymorphisms (SNPs), A-477G, T14458C (nonsynonymus SNP; Met287Thr), and T35587C, in the AS3MT gene. We compared the frequencies of the AS3MT alleles, genotypes, and haplotypes in individuals with and without skin lesions. Marginal differences in the frequencies of the Met287Thr genotype were identified between individuals with and without premalignant skin lesions (p=0.055): individuals carrying the C (TC+CC) allele (Thr) were at risk [odds ratio=4.28; 95% confidence interval (1.0-18.5)]. Also, individuals with C allele of Met287Thr displayed greater percentage of MAs in urine and decrease in the percentage of DMAs. These findings indicate that Met287Thr influences the susceptibility to premalignant As skin lesions and might be at increased risk for other adverse health effects of iAs exposure.

Blood pressure, left ventricular geometry, and systolic function in children exposed to inorganic arsenic.

BACKGROUND: Inorganic arsenic (iAs) is a ubiquitous element present in the groundwater worldwide. Cardiovascular effects related to iAs exposure have been studied extensively in adult populations. Few epidemiological studies have been focused on iAs exposure-related cardiovascular disease in children. OBJECTIVE: In this study we investigated the association between iAs exposure, blood pressure (BP), and functional and anatomical echocardiographic parameters in children. METHODS: A cross-sectional study of 161 children between 3 and 8 years was conducted in Central Mexico. The total concentration of arsenic (As) species in urine (U-tAs) was determined by hydride generation-cryotrapping-atomic absorption spectrometry and lifetime iAs exposure was estimated by multiplying As concentrations measured in drinking water by the duration of water consumption in years (LAsE). BP was measured by standard protocols, and M-mode echocardiographic parameters were determined by ultrasonography. RESULTS: U-tAs concentration and LAsE were significantly associated with diastolic (DBP) and systolic blood pressure (SBP) in multivariable linear regression models: DBP and SBP were 0.013 (95% CI: 0.002, 0.024) and 0.021 (95% CI: 0.004, 0.037) mmHg higher in association with each 1-ng/mL increase in U-tAs (p < 0.025), respectively. Left ventricular mass (LVM) was significantly associated with LAsE [5.5 g higher (95% CI: 0.65, 10.26) in children with LAsE > 620 compared with < 382 µg/L-year; p = 0.03] in an adjusted multivariable model. The systolic function parameters left ventricular ejection fraction (EF) and shortening fraction were 3.67% (95% CI: -7.14, -0.20) and 3.41% (95% CI: -6.44, -0.37) lower, respectively, in children with U-tAs > 70 ng/mL compared with < 35 ng/mL. CONCLUSION: Early-life exposure to iAs was significantly associated with higher BP and LVM and with lower EF in our study population of Mexican children.

Carotid intima-media thickness and plasma asymmetric dimethylarginine in Mexican children exposed to inorganic arsenic.

BACKGROUND: Arsenic exposure is a risk factor for atherosclerosis in adults, but there is little information on arsenic and early risk biomarkers for atherosclerosis in children. Carotid intima-media thickness (cIMT) is an indicator of subclinical atherosclerotic burden that has been associated with plasma asymmetric dimethylarginine (ADMA), a predictor of cardiovascular disease risk. OBJECTIVES: The aim of this study was to investigate associations of arsenic exposure with cIMT, ADMA, and endothelial adhesion molecules [soluble intercellular cell adhesion molecule-1 (sICAM-1); soluble vascular cell adhesion molecule-1 (sVCAM-1)] in children who had been exposed to environmental inorganic arsenic (iAs). METHODS: We conducted a cross-sectional study in 199 children 3-14 years of age who were residents of Zimapan, México. We evaluated cIMT using ultrasonography, and plasma lipid profiles by standard methods. We analyzed ADMA, sICAM-1, and sVCAM-1 by ELISA, and measured the concentrations of total speciated arsenic (tAs) in urine using hydride generation cryotrapping atomic absorption spectrometry. RESULTS: In the multiple linear regression model for cIMT, tAs categories were positively associated with cIMT increase. The estimated cIMT diameter was greater in 35- to 70-ng/mL and > 70-ng/mL groups (0.035 mm and 0.058 mm per 1-ng/mL increase in urinary tAs, respectively), compared with the < 35-ng/mL group. In addition to tAs level, plasma ADMA was a significant predictor of cIMT. In the adjusted regression model, cIMT, percent iAs, and plasma sVCAM-1 were significant predictors of ADMA levels (e.g., 0.419-µmol/L increase in ADMA per 1-mm increase in cIMT). CONCLUSIONS: Arsenic exposure and plasma ADMA levels were positively associated with cIMT in a population of Mexican children with environmental arsenic exposure through drinking water.