title: Genetic variation in metallothionein and metal-regulatory transcription factor 1 in relation to urinary cadmium, copper, and 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.
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA. Electronic address: sadams@fhcrc.org.
authors.forename: Scott V
authors.initials: SV
authors.lastname: Adams
authors.affiliation: Department of Plant and Environmental Sciences, New Mexico State University, Box 30003 MSC 3Q, Las Cruces, NM 88003, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Barrick
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA.
authors.forename: Emily P
authors.initials: EP
authors.lastname: Christopher
authors.affiliation: Environmental Chemistry and Technology, Wisconsin State Laboratory of Hygiene, University of Wisconsin, 2601 Agriculture Dr., Madison, WI 53718, USA.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Shafer
authors.affiliation: Public Health Science Biomarker Laboratory, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA.
authors.forename: Karen W
authors.initials: KW
authors.lastname: Makar
authors.affiliation: Public Health Science Biomarker Laboratory, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Song
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA.
authors.forename: Johanna W
authors.initials: JW
authors.lastname: Lampe
authors.affiliation: Border Epidemiology and Environmental Health Center, New Mexico State University, Box 30001 MSC 3BEC, Las Cruces, NM 88003, USA.
authors.forename: Hugo
authors.initials: H
authors.lastname: Vilchis
authors.affiliation: Department of Plant and Environmental Sciences, New Mexico State University, Box 30003 MSC 3Q, Las Cruces, NM 88003, USA.
authors.forename: April
authors.initials: A
authors.lastname: Ulery
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA.
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002104:Cadmium / Q000652:urine*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D003300:Copper / Q000652:urine*; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008668:Metallothionein / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D015032:Zinc / Q000652:urine*; D000097809:Transcription Factor MTF-1
chemical_list: D002104:Cadmium; D003300:Copper; D004247:DNA; D004268:DNA-Binding Proteins; D008668:Metallothionein; D014157:Transcription Factors; D015032:Zinc; D000097809:Transcription Factor MTF-1
keywords: Cadmium; Copper; Metal-regulatory transcription factor 1; Metallothionein; Zinc