Format

Send to

Choose Destination
Toxicol Appl Pharmacol. 2018 Jun 1;348:123-129. doi: 10.1016/j.taap.2018.03.034. Epub 2018 Apr 3.

Arsenic-gene interactions and beta-cell function in the Strong Heart Family Study.

Author information

1
Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, United States.
2
Texas Biomedical Research Institute, San Antonio, TX, United States.
3
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.
4
MedStar Health Research Institute, Hyattsville, MD, United States.
5
Missouri Breaks Industries Research, Inc., Eagle Butte, SD, United States.
6
Institute of Chemistry, University of Graz, Graz, Austria.
7
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
8
Department of Nutrition and UNC Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, United States.
9
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. Electronic address: matt.gribble@emory.edu.

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 -31.14, P = 0.02) and rs4607517 (SNP overall effect +16.61, P = 0.03; interaction effect with arsenic +27.02, P = 0.03). 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.

KEYWORDS:

Arsenicals; Diabetes; Environmental Epidemiology; Genetic Epidemiology; Pancreas; Susceptibility

PMID:
29621497
PMCID:
PMC5961497
DOI:
10.1016/j.taap.2018.03.034
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center