Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, USA; Area of Cardiometabolic and Renal Risk, Institute for Biomedical Research INCLIVA, Valencia, Spain.
Area of Cardiometabolic and Renal Risk, Institute for Biomedical Research INCLIVA, Valencia, Spain; Department of Internal Medicine, Hospital Clínico de Valencia, University of Valencia, Spain.
Environ Int. 2017 Sep;106:27-36. doi: 10.1016/j.envint.2017.05.008. Epub 2017 May 27.
The interaction of cadmium with genes involved in oxidative stress, cadmium metabolism and transport pathways on albuminuria can provide biological insight on the relationship between cadmium and albuminuria at low exposure levels.
We tested the hypothesis that specific genotypes in candidate genes may confer increased susceptibility to cadmium exposure.
Cadmium exposure was estimated by inductively coupled plasma mass spectrometry (ICPMS) in urine from 1397 men and women aged 18-85years participating in the Hortega Study, a representative sample of a general population from Spain. Urine albumin was measured by automated nephelometric immunochemistry. Abnormal albuminuria was defined as urine albumin greater than or equal to 30mg/g.
The weighted prevalence of abnormal albuminuria was 6.3%. The median level of urine cadmium was 0.39 (IQR, 0.23-0.65) μg/g creatinine. Multivariable-adjusted geometric mean ratios of albuminuria comparing the two highest to the lowest tertile of urine cadmium were 1.62 (95% CI, 1.43-1.84) and 2.94 (95% CI, 2.58-3.35), respectively. The corresponding odds ratios of abnormal albuminuria were 1.58 (0.83, 3.02) and 4.54 (2.58, 8.00). The association between urine cadmium and albuminuria was observed across all participant subgroups evaluated including participants without hypertension, diabetes or chronic kidney disease. We observed Bonferroni-corrected statistically significant interactions between urine cadmium levels and polymorphisms in gene SLC30A7 and RAC1.
Increasing urine cadmium concentrations were cross-sectionally associated with increased albuminuria in a representative sample of a general population from Spain. Genetic variation in oxidative stress and cadmium metabolism and transport genes may confer differential susceptibility to potential cadmium effects.
镉与氧化应激、镉代谢和转运途径相关的基因相互作用，可为低暴露水平下镉与蛋白尿之间的关系提供生物学见解。
我们检验了以下假设，即候选基因中的特定基因型可能会增加对镉暴露的易感性。
通过电感耦合等离子体质谱法（ICPMS）对 1397 名年龄在 18-85 岁的男性和女性尿液中的镉暴露进行估计，这些人来自西班牙一个普通人群的代表性样本。尿液白蛋白通过自动化散射免疫比浊法进行测量。异常蛋白尿定义为尿液白蛋白大于或等于 30mg/g。
异常蛋白尿的加权患病率为 6.3%。尿液镉的中位数水平为 0.39（IQR，0.23-0.65）μg/g 肌酐。与尿液镉的两个最高三分位相比，多变量调整后的蛋白尿几何平均比分别为 1.62（95%CI，1.43-1.84）和 2.94（95%CI，2.58-3.35）。异常蛋白尿的相应比值比为 1.58（0.83，3.02）和 4.54（2.58，8.00）。在评估的所有参与者亚组中，包括无高血压、糖尿病或慢性肾脏病的参与者，都观察到了尿液镉与蛋白尿之间的关联。我们观察到尿液镉水平与 SLC30A7 和 RAC1 基因多态性之间存在经 Bonferroni 校正的统计学显著交互作用。
在西班牙一个普通人群的代表性样本中，尿液镉浓度的升高与蛋白尿的增加呈横断面相关。氧化应激和镉代谢及转运基因的遗传变异可能赋予对潜在镉效应的不同易感性。
