Journal Articles

Arsenic-gene interactions and beta-cell function in the strong heart family study

April 26, 2018

Poojitha Balakrishnan, Ana Navas-Acien, Karin Haack, Dhananjay Vaidya, Jason G. Umans, Lyle G. Best, Walter Goessler, Kevin A. Francesconi, Nora Franceschini, Kari E. North, Shelley A. Cole, V. Saroja Voruganti, Matthew O.Gribble (2018). Arsenic-gene interactions and beta-cell function in the strong heart family study. Toxicology and Applied Pharmacology.

Author Affiliations

Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, United States
Texas Biomedical Research Institute, San Antonio, TX, United States
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States
Clinical and Translational Research, Johns Hopkins School of Medicine, Baltimore, MD, United States
MedStar Health Research Institute, Hyattsville, MD, United States
Missouri Breaks Industries Research, Inc., Eagle Butte, SD, United States
Institute of Chemistry, University of Graz, Graz, Austria
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
Department of Nutrition and UNC Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, United States
Department of Environmental Health, Emory University Rollins School of Public Health, Atlanta, GA, United States
Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, United States

Abstract

We explored arsenic-gene interactions influencing pancreatic beta-cell activity in the Strong Heart Family Study (SHFS). We considered 42 variants selected for associations with either beta-cell function (31 variants) or arsenic metabolism (11 variants) in the SHFS. Beta-cell function was calculated as homeostatic model – beta corrected for insulin resistance (cHOMA-B) by regressing homeostatic model – insulin resistance (HOMA-IR) on HOMA-B and adding mean HOMA-B. Arsenic exposure was dichotomized at the median of the sum of creatinine-corrected inorganic and organic arsenic species measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS). Additive GxE models for cHOMA-B were adjusted for age and ancestry, and accounted for family relationships. Models were stratified by center (Arizona, Oklahoma, North Dakota and South Dakota) and meta-analyzed. The two interactions between higher vs. lower arsenic and SNPs for cHOMA-B that were nominally significant at P < 0.05 were with rs10738708 (SNP overall effect 3.91, P = 0.56; interaction effect with arsenic 27.02, P = 0.03) and rs4607517 (SNP overall effect + 16.61, P = 0.03; interaction effect with arsenic − 31.14, P = 0.02). The corresponding genes GCK and TUSC1 suggest oxidative stress and apoptosis as possible mechanisms for arsenic impacts on beta-cell function. No interactions were Bonferroni-significant (1.16 × 10−3). Our findings are suggestive of oligogenic moderation of arsenic impacts on pancreatic β-cell endocrine function, but were not Bonferroni-significant.

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