Introduction: Zinc homeostasis is involved in numerous physiological and pathological conditions, ranging from type 1 and type 2 diabetes to memory impairment and cancer, and is determined by at least 28 genes, including 24 SLC (Solute Carrier) family members and 4 MTs (Metallothioneins). To explore the potential role of zinc homeostasis in MetS (metabolic syndrome) and IR (insulin resistance), we investigated 28 candidate genes by gene-SNPing.
Methods: A number of 1304 SNPs (single nucleotide polymorphism) were genotyped with the Affymetrix MEDISCOPE GeneChip in 483 subjects (123 cases of MetS and 360 controls) from two ethnic European populations Romanian and French (MEDIGENE collection). Genetic association was tested by logistic regression, whereas quantitative variables were tested by correlation trend test. Bonferroni correction and false discovery rate were applied.
Results: The most significant association was found with MetS and concerned 3 SNPs located on Chr10 between SLC39A12 and CACNB2 genes: rs7083207, rs17602947 and rs7903081 (Bonferroni P<0.03) with OR 2.15, 95% CI [1.5-3.0], OR 2.07, 95% CI [1.46-2.95] and OR 1.99, 95% CI [1.43-2.78], respectively. These 3 SNPs were also associated and/or correlated with the different components of MetS, notably with hypertriglyceridemia (OR 2.09, 95% CI [1.42-3.07], P<7.8×10-5), but not associated with IR, nor correlated with HOMA-IR index of IR. The most significant association with IR was found for SLC39A11 gene located on Chr17 (OR 2.95, 95% CI [1.68-5.18], Bonferroni P<0.05), which was also concordantly correlated with low HDL cholesterol and HOMA-IR.
Conclusions: Genes involved in zinc homeostasis are good determinants of MetS and IR, although different genes are implicated. SLC39A12/CACNB2 on Chr10 and SLC39A11 on Chr17 were the most concordantly associated and correlated with MetS and IR, respectively.