title: 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.
  
  
  OBJECTIVE
  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.
authors: Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
authors: Gerda
authors: G
authors: Rentschler
authors: Maria
authors: M
authors: Kippler
authors: Anna
authors: A
authors: Axmon
authors: Rubhana
authors: R
authors: Raqib
authors: Eva-Charlotte
authors: EC
authors: Ekström
authors: Staffan
authors: S
authors: Skerfving
authors: Marie
authors: M
authors: Vahter
authors: Karin
authors: K
authors: Broberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001118:Argentina; D001459:Bangladesh; D002104:Cadmium / Q000652:urine*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004781:Environmental Exposure; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D005838:Genotype; D006706:Homeostasis; D006801:Humans; D007118:Immunoassay; D007501:Iron / Q000097:blood; D013058:Mass Spectrometry; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D002104:Cadmium; D007501:Iron