Department of Occupational Health, School of Public Health, Fudan University, Shanghai, China.
Toxicol Appl Pharmacol. 2012 Dec 15;265(3):373-9. doi: 10.1016/j.taap.2012.09.006. Epub 2012 Sep 17.
Cadmium (Cd) toxicity of the kidney varies between individuals despite similar exposure levels. In humans Cd is mainly bound to metallothioneins (MT), which scavenge its toxic effects. Here we analyzed whether polymorphisms in MT genes MT1A and MT2A influence Cd-related kidney damage.
In a cross-sectional study N=512 volunteers were selected from three areas in South-Eastern China, which to varying degree were Cd-polluted from a smelter (control area [median Cd in urine U-Cd=2.67 μg/L], moderately [U-Cd=4.23 μg/L] and highly [U-Cd=9.13 μg/L] polluted areas). U-Cd and blood Cd (B-Cd) concentrations were measured by graphite-furnace atomic absorption spectrometry. MT1A rs11076161 (G/A), MT2A rs10636 (G/C) and MT2A rs28366003 (A/G) were determined by Taqman assays; urinary N-Acetyl-beta-(D)-Glucosaminidase (UNAG) by spectrometry, and urinary β2-microglobulin (UB2M) by ELISA.
Higher B-Cd (natural log-transformed) with increasing number of MT1A rs11076161 A-alleles was found in the highly polluted group (p-value trend=0.033; all p-values adjusted for age, sex, and smoking). In a linear model a significant interaction between rs11076161 genotype and B-Cd was found for UNAG (p=0.001) and UB2M concentrations (p=0.001). Carriers of the rs11076161 AA genotype showed steeper slopes for the associations between Cd in blood and natural log-transformed UB2M (β=1.2, 95% CI 0.72-1.6) compared to GG carriers (β=0.30, 95% CI 0.15-0.45). Also for UNAG (natural log-transformed) carriers of the AA genotype had steeper slopes (β=0.55, 95% CI 0.27-0.84) compared to GG carriers (β=0.018, 95% CI -0.79-0.11).
MT1A rs11076161 was associated with B-Cd concentrations and Cd-induced kidney toxicity at high exposure levels.
尽管暴露水平相似，但镉（Cd）对肾脏的毒性在个体之间存在差异。在人体中，Cd 主要与金属硫蛋白（MT）结合，MT 可清除其毒性作用。在这里，我们分析了 MT 基因 MT1A 和 MT2A 的多态性是否影响 Cd 相关的肾脏损伤。
在一项横断面研究中，我们从中国东南部的三个地区（冶炼厂所在的对照区[尿中 Cd 浓度 U-Cd=2.67μg/L]、中度污染区[U-Cd=4.23μg/L]和高度污染区[U-Cd=9.13μg/L]）中选择了 512 名志愿者。通过石墨炉原子吸收光谱法测量尿 Cd（U-Cd）和血 Cd（B-Cd）浓度。MT1A rs11076161（G/A）、MT2A rs10636（G/C）和 MT2A rs28366003（A/G）通过 Taqman 检测确定；通过光谱法测量尿 N-乙酰-β-（D）-氨基葡萄糖苷酶（UNAG），通过 ELISA 测量尿β2-微球蛋白（UB2M）。
在高度污染组中，随着 MT1A rs11076161 A 等位基因数量的增加，B-Cd（自然对数转换）升高（p 值趋势=0.033；所有 p 值均经年龄、性别和吸烟调整）。在线性模型中，rs11076161 基因型与 B-Cd 之间存在显著的交互作用，与 UNAG（p=0.001）和 UB2M 浓度（p=0.001）相关。与 GG 携带者相比，rs11076161 AA 基因型携带者的血液 Cd 与自然对数转换 UB2M 之间的关联斜率更陡（β=1.2，95%CI 0.72-1.6）。对于 UNAG（自然对数转换），AA 基因型携带者的斜率也更陡（β=0.55，95%CI 0.27-0.84），而 GG 携带者的斜率则较平缓（β=0.018，95%CI-0.79-0.11）。
MT1A rs11076161 与高暴露水平下的 B-Cd 浓度和 Cd 诱导的肾脏毒性相关。
