Common Variants and Haplotypes in the TF, TNF-α, and TMPRSS6 Genes Are Associated with Iron Status in a Female Black South African Population

J Nutr. 2015 May;145(5):945-53. doi: 10.3945/jn.114.209148. Epub 2015 Mar 25.

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.

Objectives: 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.

Keywords: African population; anemia; genetic variants; iron deficiency; iron status; polymorphisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Anemia, Iron-Deficiency / blood
  • Anemia, Iron-Deficiency / genetics*
  • Anemia, Iron-Deficiency / metabolism
  • Black People
  • Cohort Studies
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Histocompatibility Antigens Class II / genetics*
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Middle Aged
  • Nutritional Status
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Receptors, Transferrin / blood
  • Receptors, Transferrin / chemistry
  • Serine Endopeptidases / genetics*
  • Serine Endopeptidases / metabolism
  • Solubility
  • South Africa
  • Transferrin / analysis
  • Transferrin / genetics*
  • Transferrin / metabolism
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Histocompatibility Antigens Class II
  • Membrane Proteins
  • NFKBIL1 protein, human
  • Receptors, Transferrin
  • TNF protein, human
  • Transferrin
  • Tumor Necrosis Factor-alpha
  • Serine Endopeptidases
  • TMPRSS6 protein, human