Ethnic, Geographic, and Genetic Differences in Arsenic Metabolism at Low Arsenic Exposure: A Preliminary Analysis in the Multi-Ethnic Study of Atherosclerosis (MESA)

Poojitha Balakrishnan¹, Miranda R Jones², Dhananjay Vaidya³, Maria Tellez-Plaza^{4

5}, Wendy S Post^{6

7}, Joel D Kaufman⁸, Suzette J Bielinski⁹, Kent Taylor¹⁰, Kevin Francesconi¹¹, Walter Goessler¹², Ana Navas-Acien^{13

14

15}

Affiliations

¹ Department of Environmental Health Sciences, Columbia Mailman School of Public Health, New York, NY 10032, USA. pbalakr2@jhu.edu.
² Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. mjone132@jhu.edu.
³ Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. dvaidya1@jhmi.edu.
⁴ Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. mtellezp@gmail.com.
⁵ Fundación de Investigación Hospital Clínico de Valencia INCLIVA, Valencia 46010, Spain. mtellezp@gmail.com.
⁶ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. wpost@jhmi.edu.
⁷ Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. wpost@jhmi.edu.
⁸ Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA. joelk@uw.edu.
⁹ Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA. bielinski.suzette@mayo.edu.
¹⁰ Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Los Angeles, CA 90502, USA. ktaylor@labiomed.org.
¹¹ Institute of Chemistry, University of Graz, 8010 Graz, Austria. kevin.francesconi@uni-graz.at.
¹² Institute of Chemistry, University of Graz, 8010 Graz, Austria. walter.goessler@uni-graz.at.
¹³ Department of Environmental Health Sciences, Columbia Mailman School of Public Health, New York, NY 10032, USA. an2737@cumc.columbia.edu.
¹⁴ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. an2737@cumc.columbia.edu.
¹⁵ Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. an2737@cumc.columbia.edu.

PMID: 29874848
PMCID: PMC6025014
DOI: 10.3390/ijerph15061179

Multicenter Study

Ethnic, Geographic, and Genetic Differences in Arsenic Metabolism at Low Arsenic Exposure: A Preliminary Analysis in the Multi-Ethnic Study of Atherosclerosis (MESA)

Poojitha Balakrishnan et al. Int J Environ Res Public Health. 2018.

. 2018 Jun 5;15(6):1179.

doi: 10.3390/ijerph15061179.

Authors

Affiliations

¹ Department of Environmental Health Sciences, Columbia Mailman School of Public Health, New York, NY 10032, USA. pbalakr2@jhu.edu.
² Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. mjone132@jhu.edu.
³ Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. dvaidya1@jhmi.edu.
⁴ Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. mtellezp@gmail.com.
⁵ Fundación de Investigación Hospital Clínico de Valencia INCLIVA, Valencia 46010, Spain. mtellezp@gmail.com.
⁶ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. wpost@jhmi.edu.
⁷ Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. wpost@jhmi.edu.
⁸ Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA. joelk@uw.edu.
⁹ Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA. bielinski.suzette@mayo.edu.
¹⁰ Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Los Angeles, CA 90502, USA. ktaylor@labiomed.org.
¹¹ Institute of Chemistry, University of Graz, 8010 Graz, Austria. kevin.francesconi@uni-graz.at.
¹² Institute of Chemistry, University of Graz, 8010 Graz, Austria. walter.goessler@uni-graz.at.
¹³ Department of Environmental Health Sciences, Columbia Mailman School of Public Health, New York, NY 10032, USA. an2737@cumc.columbia.edu.
¹⁴ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. an2737@cumc.columbia.edu.
¹⁵ Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. an2737@cumc.columbia.edu.

PMID: 29874848
PMCID: PMC6025014
DOI: 10.3390/ijerph15061179

Abstract

We investigated the effect of candidate variants in AS3MT (arsenic (III) methyltransferase) with urinary arsenic metabolites and their principal components in a subset of 264 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Urinary arsenic species, including inorganic arsenic (iAs), monomethylarsonate (MMA), dimethylarsinate (DMA), and arsenobetaine (Ab), were measured using high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS) and corrected for organic sources from seafood consumption by regressing Ab on arsenic species using a validated method. Principal components of arsenic metabolism were also used as independent phenotypes. We conducted linear regression of arsenic traits with allelic dosage of candidate single nucleotide polymorphisms (SNPs) rs12768205 (G > A), rs3740394 (A > G), and rs3740393 (G > C) measured using Illumina MetaboChip. Models were stratified by non-Hispanic white vs. all other race/ethnicity and adjusted for age, sex, arsenic exposure, study site, and population stratification. Consistent with previous studies, rs12768205 showed evidence for strongest association (non-Hispanic white: iAs% -0.14 (P 0.83), MMA% -0.66 (0.49), DMA% 0.81(0.49); other race/ethnicity: 0.13 (0.71), -1.21 (0.09), 1.08 (0.20)). No association, however, passed the strict Bonferroni p-value. This was a novel study among an ethnically diverse population exposed to low arsenic levels.

Keywords: AS3MT; MESA; arsenic; epidemiology; genetic susceptibility; geography; methylation.

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Conflict of interest statement

The authors declare no conflict of interest.

References

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Ethnic, Geographic, and Genetic Differences in Arsenic Metabolism at Low Arsenic Exposure: A Preliminary Analysis in the Multi-Ethnic Study of Atherosclerosis (MESA)

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Ethnic, Geographic, and Genetic Differences in Arsenic Metabolism at Low Arsenic Exposure: A Preliminary Analysis in the Multi-Ethnic Study of Atherosclerosis (MESA)

Authors

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Abstract

Conflict of interest statement

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