金属硫蛋白和金属调节转录因子1的基因变异与尿镉、铜和锌的关系。
Genetic variation in metallothionein and metal-regulatory transcription factor 1 in relation to urinary cadmium, copper, and zinc.
作者信息
Adams Scott V, Barrick Brian, Christopher Emily P, Shafer Martin M, Makar Karen W, Song Xiaoling, Lampe Johanna W, Vilchis Hugo, Ulery April, Newcomb Polly A
机构信息
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA.
Department of Plant and Environmental Sciences, New Mexico State University, Box 30003 MSC 3Q, Las Cruces, NM 88003, USA.
出版信息
Toxicol Appl Pharmacol. 2015 Dec 15;289(3):381-8. doi: 10.1016/j.taap.2015.10.024. Epub 2015 Oct 31.
BACKGROUND
Metallothionein (MT) proteins play critical roles in the physiological handling of both essential (Cu and Zn) and toxic (Cd) metals. MT expression is regulated by metal-regulatory transcription factor 1 (MTF1). Hence, genetic variation in the MT gene family and MTF1 might influence excretion of these metals.
METHODS
321 women were recruited in Seattle, WA and Las Cruces, NM and provided demographic information, urine samples for measurement of metal concentrations by mass spectrometry and creatinine, and blood or saliva for extraction of DNA. Forty-one single nucleotide polymorphisms (SNPs) within the MTF1 gene region and the region of chromosome 16 encoding the MT gene family were selected for genotyping in addition to an ancestry informative marker panel. Linear regression was used to estimate the association of SNPs with urinary Cd, Cu, and Zn, adjusted for age, urinary creatinine, smoking history, study site, and ancestry.
RESULTS
Minor alleles of rs28366003 and rs10636 near the MT2A gene were associated with lower urinary Cd, Cu, and Zn. Minor alleles of rs8044719 and rs1599823, near MT1A and MT1B, were associated with lower urinary Cd and Zn, respectively. Minor alleles of rs4653329 in MTF1 were associated with lower urinary Cd.
CONCLUSIONS
These results suggest that genetic variation in the MT gene region and MTF1 influences urinary Cd, Cu, and Zn excretion.
背景
金属硫蛋白（MT）在必需金属（铜和锌）和有毒金属（镉）的生理处理过程中发挥着关键作用。MT的表达受金属调节转录因子1（MTF1）调控。因此，MT基因家族和MTF1的基因变异可能会影响这些金属的排泄。
方法
在华盛顿州西雅图市和新墨西哥州拉斯克鲁塞斯市招募了321名女性，她们提供了人口统计学信息、用于通过质谱法测量金属浓度和肌酐的尿液样本，以及用于提取DNA的血液或唾液样本。除了一个祖先信息标记面板外，还选择了MTF1基因区域和16号染色体上编码MT基因家族区域内的41个单核苷酸多态性（SNP）进行基因分型。使用线性回归来估计SNP与尿镉、铜和锌之间的关联，并对年龄、尿肌酐、吸烟史、研究地点和祖先进行了调整。
结果
MT2A基因附近的rs28366003和rs10636的次要等位基因与较低的尿镉、铜和锌水平相关。MT1A和MT1B附近的rs8044719和rs1599823的次要等位基因分别与较低的尿镉和锌水平相关。MTF1中rs4653329的次要等位基因与较低的尿镉水平相关。
结论
这些结果表明，MT基因区域和MTF1的基因变异会影响尿镉、铜和锌的排泄。
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