Introduction and Objective: The widely prevalent C variant of SNP rs13266634, encoding an amino acid exchange in the ß-cell specific zinc (Zn) transporter ZnT8, is associated with type 2 diabetes. The relationship between Zn status, ZnT8 genotype at rs13266634, and ß-cell function is underexplored.Methods: Zn concentration in urine samples -uZn, a proxy for Zn status- in a randomly selected sub-cohort of mothers from the Hyperglycemia and Adverse Pregnancy Outcome Follow Up Study (HAPO-FUS) cohort was measured using ICP-MS.Results: uZn alone was negatively associated with HOMA2-β (Model 1). When ZnT8 genotype was examined alone (Model 2), HOMA2-β of mothers with T/T but not C/T genotype was significantly higher than those with C/C genotype. When combining uZn and ZnT8 genotype in the same model, there was a stronger negative association between uZn and HOMA2-β in mothers (Model 3). This suggests a modifying effect of ZnT8 genotype on the association between uZn and HOMA2-β. To further examine this, we added an interaction term ZnT8 X uZn to the model. Here, we found a significant association of HOMA2-β with the interaction term T/T genotype X uZn as well as a significant association with the T/T genotype itself and a negative association with uZn (Model 4).Conclusion: Taken together, these results provide evidence that ZnT8 genotype modifies the association between Zn status and HOMA2-β -a marker of ß-cell function.
M. El Muayed: None. J.C. Wang: None. K. Dennehy: None. O. Chepurny: None. M. Hayes: None. W.L. Lowe: None. D. Wang: None.
1U01DK094830 from the National Institute of Diabetes and Digestive and Kidney Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. 5R01ES027011 from the National Institutes of Health/National Institute of Environmental Health Sciences
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