Cadmium concentrations in human blood and urine are associated with polymorphisms in zinc transporter genes

Bakground. Variation in susceptibility to cadmium (Cd) toxicity may partly be due to differences in Cd toxicokinetics. Experimental studies indicate that zinc (Zn) homeostasis proteins transport Cd. Objective. To evaluate the potential effect of variation in Zn-transporter genes (SLC39A8 and SLC39A14) on Cd concentrations in blood and urine. Methods. We studied women from the Argentinean Andes [ median urinary Cd concentration (U-Cd) = 0.24 mg L (1); erythrocyte Cd (Ery-Cd) = 0.75 mu g L (1) (n = 172)] and from rural Bangladesh [U-Cd = 0.54 mu g L-1 (n = 359), Ery-Cd = 1.1 mu g L-1 (n = 400)]. Polymorphisms (n = 36) were genotyped with Sequenom. Gene expression was measured in whole blood with Illumina DirectHyb HumanHT-12 v4.0. Results. Polymorphisms in SLC39A8 and SLC39A14 were associated with Ery-Cd concentrations in the Andean population. For SLC39A14, women carrying GT or TT genotypes of rs4872479 had 1.25 [95% confidence interval (CI) = 1.07-1.46] times higher Ery-Cd than women carrying GG. Also, women carrying AG or AA of rs870215 had 1.17 (CI 1.01-1.32) times higher Ery-Cd than those carrying GG. For SLC39A8, women carrying AG or GG of rs10014145 had 1.18 (CI 1.03-1.35) times higher Ery-Cd than those with AA, and carriers of CA or AA of rs233804 showed 1.22 (CI 1.04-1.42) times higher Ery-Cd than CC. The Bangladeshi population had similar, but statistically non-significant associations between some of these SNPs and Ery-Cd. In the Andean population, the genotypes of SLC39A14 rs4872479 and rs870215 associated with lower Ery-Cd showed positive correlations with plasma-Zn (P-Zn) and SLC39A14 expression. Conclusions. Polymorphisms in SLC39A14 and SLC39A8 seemed to affect blood Cd concentrations, for SLC39A14 this effect may occur via differential gene expression.