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Author 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.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ BIOLOGICAL MARKERS ♦ BLOOD ♦ CADMIUM ♦ CHROMOSOMES ♦ COPPER ♦ CREATININE ♦ DNA ♦ ECOLOGICAL CONCENTRATION ♦ EXCRETION ♦ EXTRACTION ♦ GENETICS ♦ GENOTYPE ♦ LANTHANUM SULFIDES ♦ MASS SPECTROSCOPY ♦ METALLOTHIONEIN ♦ NUCLEOTIDES ♦ SALIVA ♦ SMOKES ♦ TOXICITY ♦ TRANSCRIPTION ♦ TRANSCRIPTION FACTORS ♦ URINE ♦ ZINC
Abstract 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. - Highlights: • Genetic variation in metallothionein (MT) genes was assessed in two diverse populations. • Single nucleotide polymorphisms (SNPs) in MT genes were associated with mean urinary Cd, Cu and Zn. • Genetic variation may influence biomarkers of exposure, and associations of exposure with health.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2015-12-15
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 289
Issue Number 3


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