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Background Hypertension and diabetes have been associated with inefficient arsenic metabolism, primarily through studies undertaken in populations exposed through drinking water. Recently, rice has been recognized as a source of arsenic exposure, but it remains unclear whether populations with high rice consumption but no known water exposure are at risk for the health problems associated with inefficient arsenic metabolism. Methods The relationships between arsenic metabolism efficiency (% inorganic arsenic, % monomethylarsenate and % dimethylarsinate in urine) and three hypertension- and seven diabetes-related traits were estimated among 12 609 participants of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). A two-sample Mendelian randomization approach incorporated genotype-arsenic metabolism relationships from literature, and genotype-trait relationships from HCHS/SOL, with a mixed-effect linear model. Analyses were stratified by rice consumption and smoking. Results Among never smokers with high rice consumption, each percentage point increase in was associated with increases of 1.96 mmHg systolic blood pressure (P = 0.034) and 1.85 mmHg inorganic arsenic diastolic blood pressure (P = 0.003). Monomethylarsenate was associated with increased systolic (1.64 mmHg/percentage point increase; P = 0.021) and diastolic (1.33 mmHg/percentage point increase; P = 0.005) blood pressure. Dimethylarsinate, a marker of efficient metabolism, was associated with lower systolic (−0.92 mmHg/percentage point increase; P = 0.025) and diastolic (-0.79 mmHg/percentage point increase; P = 0.004) blood pressure. Among low rice consumers and ever smokers, the results were consistent with no association. Evidence for a relationship with diabetes was equivocal. Conclusions Less efficient arsenic metabolism was associated with increased blood pressure among never smokers with high rice consumption, suggesting that arsenic exposure through rice may contribute to high blood pressure in the Hispanic/Latino community.

Aims The present study examined how variation in mu- (OPRM1), kappa- (OPRK), and delta- (OPRD) opioid receptor genes may influence the efficacy of naltrexone in the context of a smoking cessation trial. Methods The study’s primary objective was to examine the association of the Asn40Asp OPRM1 single nucleotide polymorphism (SNP) with naltrexone’s effects on smoking quit rate, weight gain, and heavy drinking behavior during a double-blind, randomized clinical trial in 280 adult DSM-IV nicotine-dependent participants. The secondary goal of the study was to examine the relationship of 20 additional SNPs of OPRM1, OPRK, and OPRD with the aforementioned outcomes. Results Results indicated a null association between any opioid-receptor gene SNP and naltrexone’s effects on smoking quit rate, weight gain, and heavy drinking behavior in this sample of nicotine dependent participants. Conclusions In sum, these results do not suggest that genetic variation in opioid-receptors is related to treatment responses to naltrexone in a smoking cessation trial.

Arsenic exposure through drinking water is a serious global health issue. Observational studies suggest that individuals who metabolize arsenic efficiently are at lower risk for toxicities such as arsenical skin lesions. Using two single nucleotide polymorphisms(SNPs) in the 10q24.32 region (near AS3MT) that show independent associations with metabolism efficiency, Mendelian randomization can be used to assess whether the association between metabolism efficiency and skin lesions is likely to be causal.Using data on 2060 arsenic-exposed Bangladeshi individuals, we estimated associations for two 10q24.32 SNPs with relative concentrations of three urinary arsenic species (representing metabolism efficiency): inorganic arsenic (iAs), monomethylarsonic acid(MMA) and dimethylarsinic acid (DMA). SNP-based predictions of iAs%, MMA% and DMA% were tested for association with skin lesion status among 2483 cases and 2857 controls.Causal odds ratios for skin lesions were 0.90 (95% confidence interval[CI]: 0.87, 0.95), 1.19 (CI: 1.10, 1.28) and 1.23 (CI: 1.12, 1.36)for a one standard deviation increase in DMA%, MMA% and iAs%,respectively. We demonstrated genotype-arsenic interaction, with metabolism-related variants showing stronger associations with skin lesion risk among individuals with high arsenic exposure (synergy index: 1.37; CI: 1.11, 1.62).We provide strong evidence for a causal relationship between arsenic metabolism efficiency and skin lesion risk. Mendelian randomization can be used to assess the causal role of arsenic exposure and metabolism in a wide array of health conditions.exposure and metabolism in a wide array of health conditions.Developing interventions that increase arsenic metabolism efficiency are likely to reduce the impact of arsenic exposure on health.

Elevated concentrations of arsenic in groundwater pose a public health threat to millions of people worldwide. The authors aimed to evaluate the association between arsenic exposure and skin lesion incidence among participants in the Health Effects of Arsenic Longitudinal Study (HEALS). The analyses used data on 10,182 adults free of skin lesions at baseline through the third biennial follow-up of the cohort (2000-2009). Discrete-time hazard regression models were used to estimate hazard ratios and 95% confidence intervals for incident skin lesions. Multivariate-adjusted hazard ratios for incident skin lesions comparing 10.1-50.0, 50.1-100.0, 100.1-200.0, and ≥200.1 μg/L with ≤10.0 μg/L of well water arsenic exposure were 1.17 (95% confidence interval (CI): 0.92, 1.49), 1.69 (95% CI: 1.33, 2.14), 1.97 (95% CI: 1.58, 2.46), and 2.98 (95% CI: 2.40, 3.71), respectively (P(trend) = 0.0001). Results were similar for the other measures of arsenic exposure, and the increased risks remained unchanged with changes in exposure in recent years. Dose-dependent associations were more pronounced in females, but the incidence of skin lesions was greater in males and older individuals. Chronic arsenic exposure from drinking water was associated with increased incidence of skin lesions, even at low levels of arsenic exposure (100 μg/L).

Skin lesions are classic clinical signs of toxicity due to long-term exposure to arsenic, and they are considered precursors to arsenic-related skin cancer. The authors prospectively evaluated synergisms between effects of arsenic exposure and those of tobacco use, sun exposure, and pesticide and fertilizer use on incident skin lesions using risk factor data from 5,042 men from the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh, which recruited participants from October 2000 to May 2002. Discrete time hazard models were used to estimate measures of synergistic interactions on the additive scale. The authors observed significant synergistic effects between various measures of arsenic exposure and smoking and fertilizer use. The relative excess risks for the interactions between smoking status and arsenic exposure were 0.12 (95% confidence interval: 0.06, 0.19) for water arsenic and 0.11 (95% confidence interval: 0.05, 0.15) for urinary arsenic measures, respectively. Significant synergistic effects were also observed between fertilizer use and water arsenic (relative excess risk for the interaction = 0.06, 95% confidence interval: 0.01, 0.12). This is the first prospective study based on individual-level data that supports a role for smoking and certain occupational risk factors in modification of the effect of long-term arsenic exposure on skin lesions. Understanding differential arsenic susceptibility allows researchers to develop interventions to prevent the health consequences of this massive problem in the Bangladeshi population and beyond.

Background Body mass index (BMI) (kg/m2) has a U- or J-shaped relationship with all-cause mortality in Western and East Asian populations. However, this relationship is not well characterized in Bangladesh, where the BMI distribution is shifted towards lower values. Methods Using data on 11 445 individuals (aged 18–75 years) participating in the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh, we prospectively examined associations of BMI (measured at baseline) with all-cause mortality during ∼6 years of follow-up. We also examined this relationship within strata of key covariates (sex, age, smoking, education and arsenic exposure). Cox proportional hazards models adjusted for these covariates and BMI-related illnesses were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for BMI categories defined by the World Health Organization. Results Low BMI was strongly associated with increased mortality in this cohort (P-trend < 0.0001). Severe underweight (BMI < 16 kg/m2; HR 2.06, CI 1.53–2.77) and moderate underweight (16.0–16.9 kg/m2; HR 1.39, CI 1.01–2.90) were associated with increased all-cause mortality compared with normal BMI (18.6–22.9 kg/m2). The highest BMI category (≥23.0 kg/m2) did not show a clear association with mortality (HR 1.10, CI 0.77–1.53). The BMI–mortality association was stronger among individuals with