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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.

ABSTRACT: 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.

SUBMITTER: Scannell Bryan M

PROVIDER: S-EPMC6659367 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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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.

Scannell Bryan Molly M Sofer Tamar T Mossavar-Rahmani Yasmin Y Thyagarajan Bharat B Zeng Donglin D Daviglus Martha L ML Argos Maria M

International journal of epidemiology 20190601 3

<h4>Background</h4>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.<h4>Methods</h4>The relationships between arsenic metabolism eff ...[more]

PMID: 30929011

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Project description:Five sequence variants in SLC16A11 (rs117767867, rs13342692, rs13342232, rs75418188, and rs75493593), which occur in two non-reference haplotypes, were recently shown to be associated with diabetes in Mexicans from the SIGMA consortium. We aimed to determine whether these previous findings would replicate in the HCHS/SOL Mexican origin group and whether genotypic effects were similar in other HCHS/SOL groups. We analyzed these five variants in 2492 diabetes cases and 5236 controls from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), which includes U.S. participants from six diverse background groups (Mainland groups: Mexican, Central American, and South American; and Caribbean groups: Puerto Rican, Cuban, and Dominican). We estimated the SNP-diabetes association in the six groups and in the combined sample. We found that the risk alleles occur in two non-reference haplotypes in HCHS/SOL, as in the SIGMA Mexicans. The haplotype frequencies were very similar between SIGMA Mexicans and the HCHS/SOL Mainland groups, but different in the Caribbean groups. The SLC16A11 sequence variants were significantly associated with risk for diabetes in the Mexican origin group (P?=?0.025), replicating the SIGMA findings. However, these variants were not significantly associated with diabetes in a combined analysis of all groups, although the power to detect such effects was 85% (assuming homogeneity of effects among the groups). Additional analyses performed separately in each of the five non-Mexican origin groups were not significant. We also analyzed (1) exclusion of young controls and, (2) SNP by BMI interactions, but neither was significant in the HCHS/SOL data. The previously reported effects of SLC16A11 variants on diabetes in Mexican samples was replicated in a large Mexican-American sample, but these effects were not significant in five non-Mexican Hispanic/Latino groups sampled from U.S. populations. Lack of replication in the HCHS/SOL non-Mexicans, and in the entire HCHS/SOL sample combined may represent underlying genetic heterogeneity. These results indicate a need for future genetic research to consider heterogeneity of the Hispanic/Latino population in the assessment of disease risk, but add to the evidence suggesting SLC16A11 as a potential therapeutic target for type 2 diabetes.

Dataset Information

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.

Publications

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.

Similar Datasets

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