Genetic variation in metallothionein and metal-regulatory transcription factor 1 in relation to urinary cadmium, copper, and zinc
Journal Article
·
· Toxicology and Applied Pharmacology
- Department of Plant and Environmental Sciences, New Mexico State University, Box 30003 MSC 3Q, Las Cruces, NM 88003 (United States)
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109 (United States)
- Environmental Chemistry and Technology, Wisconsin State Laboratory of Hygiene, University of Wisconsin, 2601 Agriculture Dr., Madison, WI 53718 (United States)
- Public Health Science Biomarker Laboratory, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109 (United States)
- Border Epidemiology and Environmental Health Center, New Mexico State University, Box 30001 MSC 3BEC, Las Cruces, NM 88003 (United States)
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.
- OSTI ID:
- 22687843
- Journal Information:
- Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 289; ISSN TXAPA9; ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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