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Portrait photo of Gerda Rentschler

Gerda Rentschler

Project Coordinator

Portrait photo of Gerda Rentschler

Polymorphisms in Iron Homeostasis Genes and Urinary Cadmium Concentrations among Nonsmoking Women in Argentina and Bangladesh.

Author

  • Gerda Rentschler
  • Maria Kippler
  • Anna Axmon
  • Rubhana Raqib
  • Eva-Charlotte Ekström
  • Staffan Skerfving
  • Marie Vahter
  • Karin Broberg Palmgren

Summary, in English

BACKGROUND: Cadmium (Cd) is a human toxicant and carcinogen. Genetic variation might affect long-term accumulation. Cadmium is absorbed by iron transporters. OBJECTIVES: To evaluate the impact of iron homeostasis genes (divalent metal transporter 1 SLC11A2; transferrin TF; transferrin receptors TFR2 and TFRC; ferroportin SLC40A1) on Cd accumulation. METHODS: Subjects were non-smoking women living in the Argentinean Andes [n=172; median urinary Cd (U-Cd)=0.24 µg/L] and Bangladesh (n=359; U-Cd=0.53 µg/L) with Cd exposure mainly from food. U-Cd and Cd in whole blood or erythrocytes (Ery-Cd) was measured by ICPMS. Fifty polymorphisms were genotyped by Sequenom. Gene expression was measured in whole blood (n=72) with Illumina DirectHyb HumanHT-12 v4.0. RESULTS: TFRC rs3804141 was consistently associated with U-Cd. In the Andeans, mean U-Cd concentrations were 22% (95% CI: -2, 51%) and 56% (95% CI: 10, 120%) higher in women with GA and AA genotypes, respectively, relative to women with the GG genotype. In Bangladesh, mean U-Cd concentrations were 22% (95% CI: 1, 48%) and 58% (95% CI: -3, 157%) higher in women with GA and AA versus GG genotype, respectively (adjusted for age and plasma ferritin in both groups; p for trend 0.006 [Andes] and 0.009 [Bangladesh]). TFRC expression in blood was negatively correlated with plasma ferritin (rS=-0.33, p=0.006), and positively correlated with Ery-Cd (significant at ferritin concentrations <30 µg/L only, rS=0.40, p=0.046). Rs3804141 did not modify these associations or predict TFRC expression. Cd was not consistently associated with any of the other polymorphisms evaluated. CONCLUSIONS: One TFRC polymorphism was associated with urine Cd concentration, a marker of Cd accumulation in the kidney, in two very different populations. The consistency of the findings supports the possibility of a causal association.

Department/s

  • Division of Occupational and Environmental Medicine, Lund University

Publishing year

2013

Language

English

Pages

467-472

Publication/Series

Environmental Health Perspectives

Volume

121

Issue

4

Document type

Journal article

Publisher

National Institute of Environmental Health Sciences

Topic

  • Environmental Health and Occupational Health

Status

Published

ISBN/ISSN/Other

  • ISSN: 1552-9924