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

Abstract

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.

Anthroposophic lifestyle influences the concentration of metals in placenta and cord blood

“…Interestingly, we also found significantly higher concentrations of the essential element Co in maternal blood, placenta and cord blood in the anthroposophic group. The strong positive correlations with Cd in both maternal blood and placenta, and the inverse association with iron in the placenta, give support to earlier reports on similar transport mechanisms for these metals (Gunshin et al, 1997;Meltzer et al, 2010;Rentschler et al, 2013). However, in contrast to Cd, the cord blood concentrations of Co were similar to those in maternal blood irrespective of lifestyle; and both were generally low, o0.1 mg/kg.…”

Cadmium Exposure and Clinical Cardiovascular Disease: A Systematic Review

“…In 2,926 adult twins living in Australia, suggestive linkage peaks related to red blood cell cadmium levels were found in chromosomes 2, 18, 20, and X [91]. One polymorphism in the transferrin receptor gene was consistently associated to urine cadmium levels in non smoking women from Argentina (N=172) and Bangladesh (N=359)[92]. In 370 individuals from Thailand, polymorphisms of the glutathione S-transferases were associated to blood cadmium concentrations [93].…”

Physiology of Iron Metabolism

“…Several groups reported on the genetic polymorphism of the proteins involved in iron homeostasis, but not related to iron deficiency or overload [116,117,118]. Genetic analysis of iron deficiency in mice has been evaluated [119].…”