title: Common Variants and Haplotypes in the TF, TNF-α, and TMPRSS6 Genes Are Associated with Iron Status in a Female Black South African Population.
abstract: BACKGROUND
  It is unknown whether single nucleotide polymorphisms (SNPs), associated with iron status in European and Asian populations, have the same relation within the African population.
  
  
  OBJECTIVE
  We investigated associations of reported SNPs with iron markers in a South African cohort.
  
  
  METHODS
  Hemoglobin concentration, serum ferritin (SF) and soluble transferrin receptor (sTfR) concentrations, and body iron (BI) stores were measured in women (n = 686; range, 32-86 y) who were part of the Prospective Urban and Rural Epidemiology study. Thirty-two SNPs in 12 genes were selected based on existing genome-wide association study data.
  
  
  RESULTS
  In the transferrin (TF) gene, SF and BI were significantly lower in the heterozygote genotype (AG) of reference SNP (rs) 1799852 (P = 0.01 and 0.03, respectively) and sTfR concentrations were significantly higher (P = 0.004) than the homozygote minor allele genotype (AA), whereas transferrin receptor and BI concentrations were significantly lower in the heterozygote genotype (AG) of rs3811647 (both P = 0.03) than the homozygote wild-type (AA) and minor allele groups (GG). The chromosome 6 allele combination (AAA) consisting of rs1799964 and rs1800629 both in tumor necrosis factor-α (TNF-α) and rs2071592 in nuclear factor κB inhibitor-like protein 1 (NFKBIL1) was associated with higher odds for low SF concentrations (SF < 15 μg/L; OR: 1.86; 95% CI: 1.23, 2.79) than the allele combinations AGA, GGT, and AGT. The chromosome 22 allele combination (GG) consisting of rs228918 and rs228921 in the transmembrane protease serine 6 (TMPRSS6) gene was associated with lower odds for increased sTfR concentrations (sTfR > 8.3mg/L; OR: 0.79; 95% CI: 0.63, 0.98) than the allele combination AA.
  
  
  CONCLUSIONS
  Various SNPs and allele combinations in the TF, TNF-α, and TMPRSS6 genes are associated with iron status in black South African women; however, these association patterns are different compared with European ancestry populations. This stresses the need for population-specific genomic data.
authors: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands;
authors: Wanjiku N
authors: WN
authors: Gichohi-Wainaina
authors: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands; alida.melse@wur.nl.
authors: Alida
authors: A
authors: Melse-Boonstra
authors: The Laboratory of Genetic, Endocrine, and Metabolic Diseases, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands;
authors: Dorine W
authors: DW
authors: Swinkels
authors: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands; Laboratory of Human Nutrition, Institute of Food Nutrition and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology, Zurich, Switzerland; and.
authors: Michael B
authors: MB
authors: Zimmermann
authors: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands;
authors: Edith J
authors: EJ
authors: Feskens
authors: Center of Excellence for Nutrition, North-West University, Potchefstroom, South Africa.
authors: G Wayne
authors: GW
authors: Towers
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D044383:Black People; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009752:Nutritional Status; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011990:Receptors, Transferrin / Q000097:blood / Q000737:chemistry; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D012995:Solubility; D013019:South Africa; D014168:Transferrin / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; C120111:NFKBIL1 protein, human; D011990:Receptors, Transferrin; C439524:TNF protein, human; D014168:Transferrin; D014409:Tumor Necrosis Factor-alpha; D012697:Serine Endopeptidases; C504318:TMPRSS6 protein, human
keywords: African population; anemia; genetic variants; iron deficiency; iron status; polymorphisms