Rentschler Gerda, Kippler Maria, Axmon Anna, Raqib Rubhana, Skerfving Staffan, Vahter Marie, Broberg Karin
Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
Metallomics. 2014 Apr;6(4):885-91. doi: 10.1039/c3mt00365e.
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.
To evaluate the potential effect of variation in Zn-transporter genes (SLC39A8 and SLC39A14) on Cd concentrations in blood and urine.
We studied women from the Argentinean Andes [median urinary Cd concentration (U-Cd) = 0.24 μg L(-1); erythrocyte Cd (Ery-Cd) = 0.75 μg L(-1) (n = 172)] and from rural Bangladesh [U-Cd = 0.54 μg L(-1) (n = 359), Ery-Cd = 1.1 μg 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.
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.
Polymorphisms in SLC39A14 and SLC39A8 seemed to affect blood Cd concentrations, for SLC39A14 this effect may occur via differential gene expression.
对镉（Cd）毒性的易感性差异可能部分归因于镉毒代动力学的差异。实验研究表明，锌（Zn）稳态蛋白可转运镉。
评估锌转运蛋白基因（SLC39A8和SLC39A14）变异对血液和尿液中镉浓度的潜在影响。
我们研究了来自阿根廷安第斯地区的女性[尿镉浓度中位数（U-Cd）=0.24μg/L；红细胞镉（Ery-Cd）=0.75μg/L（n = 172）]以及来自孟加拉国农村的女性[U-Cd = 0.54μg/L（n = 359），Ery-Cd = 1.1μg/L（n = 400）]。使用Sequenom对36个多态性进行基因分型。采用Illumina DirectHyb HumanHT-12 v4.0在全血中测量基因表达。
SLC39A8和SLC39A14中的多态性与安第斯人群的红细胞镉浓度相关。对于SLC39A14，携带rs4872479的GT或TT基因型的女性红细胞镉浓度比携带GG基因型的女性高1.25倍[95%置信区间（CI）=1.07 - 1.46]。此外，携带rs870215的AG或AA基因型的女性红细胞镉浓度比携带GG基因型的女性高1.17倍（CI 1.01 - 1.32）。对于SLC39A8，携带rs10014145的AG或GG基因型的女性红细胞镉浓度比携带AA基因型的女性高1.18倍（CI 1.03 - 1.35），携带rs233804的CA或AA基因型的女性红细胞镉浓度比CC基因型高1.22倍（CI 1.04 - 1.42）。孟加拉人群中，这些单核苷酸多态性（SNP）与红细胞镉之间存在相似但无统计学意义的关联。在安第斯人群中，与较低红细胞镉相关的SLC39A14 rs4872479和rs870215基因型与血浆锌（P-Zn）和SLC39A14表达呈正相关。
SLC39A14和SLC39A8中的多态性似乎会影响血液中的镉浓度，对于SLC39A14，这种影响可能通过差异基因表达发生。
