Portal de Periódicos da CAPES

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

2018; Elsevier BV; Volume: 348; Linguagem: Inglês

10.1016/j.taap.2018.03.034

1096-0333

Poojitha Balakrishnan, Ana Navas‐Acién, 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,

Arsenic contamination and mitigation

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