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Polymorphisms in Iron Homeostasis Genes and Urinary Cadmium Concentrations among Nonsmoking Women in Argentina and Bangladesh
Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Sweden.
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Sweden.
International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh (icddr,b).
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2013 (English)In: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 121, no 4, 467-472 p.Article in journal (Refereed) Published
Abstract [en]

Background:

Cadmium (Cd) is a human toxicant and carcinogen. Genetic variation might affect long-term accumulation. Cd is absorbed via iron transporters.

Objectives:

We evaluated the impact of iron homeostasis genes [divalent metal transporter 1 (SLC11A2), transferrin (TF), transferrin receptors (TFR2 and TFRC), and ferroportin (SLC40A1)] on Cd accumulation.

Methods:

Subjects were nonsmoking women living in the Argentinean Andes [n = 172; median urinary Cd (U-Cd) = 0.24 µg/L] and Bangladesh (n = 359; U-Cd = 0.54 µg/L) with Cd exposure mainly from food. Concentrations of U-Cd and Cd in whole blood or in erythrocytes (Ery-Cd) were measured by inductively coupled plasma mass spectrometry. 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 Andean women, mean U-Cd concentrations were 22% (95% CI: –2, 51%), and they were 56% (95% CI: 10, 120%) higher in women with GA and AA genotypes, respectively, relative to women with the GG genotype. In the Bangladeshi women, mean U-Cd concentrations were 22% (95% CI: 1, 48%), and they were 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; ptrend = 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 of < 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.

Place, publisher, year, edition, pages
2013. Vol. 121, no 4, 467-472 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-198262DOI: 10.1289/ehp.1205672ISI: 000323706100031PubMedID: 23416510OAI: oai:DiVA.org:uu-198262DiVA: diva2:615572
Available from: 2013-04-11 Created: 2013-04-11 Last updated: 2017-12-06Bibliographically approved

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Ekström, Eva-Charlotte

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