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

by Umans, Jason G.
Citation: Toxicology & Applied Pharmacology. 348:123-129, 2018 Apr 03.Journal: Toxicology and applied pharmacology.Published: 2018ISSN: 0041-008X.Full author list: Balakrishnan P; Navas-Acien A; Haack K; Vaidya D; Umans JG; Best LG; Goessler W; Francesconi KA; Franceschini N; North KE; Cole SA; Voruganti VS; Gribble MO.UI/PMID: 29621497.Institution(s): MedStar Health Research Instituteason GActivity type: Journal Article.Medline article type(s): Journal ArticleDigital Object Identifier: (Click here) Abbreviated citation: Toxicol Appl Pharmacol. 348:123-129, 2018 Apr 03.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 (1.16x10<sup>-3</sup>). Our findings are suggestive of oligogenic moderation of arsenic impacts on pancreatic beta-cell endocrine function, but were not Bonferroni-significant.Abstract: Copyright (c) 2018 Elsevier Inc. All rights reserved.

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