Mendelian randomization of inorganic arsenic metabolism as a risk factor for hypertension- and diabetes-related traits among adults in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) cohort

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 12609 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.