Common variants and haplotypes in the TF, TNF-a, and TMPRSS6 genes are associated with iron status in a female black South African population

W.N. Gichohi-Wainaina, A. Boonstra, D.W. Swinkels, M.B. Zimmermann, E.J.M. Feskens, G.W. Towers

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)

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 aimed to investigate associations of reported SNPs with iron markers in a South African cohort. Methods: Blood concentrations of hemoglobin, serum ferritin (SF), serum soluble transferrin receptor (sTfR), and body iron (BI) stores were determined from 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-a (TNF-a) and rs2071592 in nuclear factor ¿B 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-a, 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.
Original languageEnglish
Pages (from-to)945-953
JournalThe Journal of Nutrition
Volume145
Issue number5
DOIs
Publication statusPublished - 2015

Fingerprint

Transferrin
Haplotypes
Iron
Tumor Necrosis Factor-alpha
Single Nucleotide Polymorphism
Alleles
Transferrin Receptors
Ferritins
Population
Genes
Serum
Genotype
Homozygote
Heterozygote
Apoferritins
Metagenomics
Chromosomes, Human, Pair 6
Genome-Wide Association Study
Hemoglobins
Epidemiology

Keywords

  • tumor-necrosis-factor
  • transferrin g277s mutation
  • deficiency anemia
  • serum hepcidin
  • women
  • risk
  • disease
  • hfe
  • polymorphisms
  • saturation

Cite this

@article{bc7b913e8f28487bb3c445b9d23b4846,
title = "Common variants and haplotypes in the TF, TNF-a, 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. Objectives: We aimed to investigate associations of reported SNPs with iron markers in a South African cohort. Methods: Blood concentrations of hemoglobin, serum ferritin (SF), serum soluble transferrin receptor (sTfR), and body iron (BI) stores were determined from 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-a (TNF-a) and rs2071592 in nuclear factor ¿B 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-a, 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 = "tumor-necrosis-factor, transferrin g277s mutation, deficiency anemia, serum hepcidin, women, risk, disease, hfe, polymorphisms, saturation",
author = "W.N. Gichohi-Wainaina and A. Boonstra and D.W. Swinkels and M.B. Zimmermann and E.J.M. Feskens and G.W. Towers",
year = "2015",
doi = "10.3945/jn.114.209148",
language = "English",
volume = "145",
pages = "945--953",
journal = "The Journal of Nutrition",
issn = "0022-3166",
publisher = "American Society for Nutrition",
number = "5",

}

Common variants and haplotypes in the TF, TNF-a, and TMPRSS6 genes are associated with iron status in a female black South African population. / Gichohi-Wainaina, W.N.; Boonstra, A.; Swinkels, D.W.; Zimmermann, M.B.; Feskens, E.J.M.; Towers, G.W.

In: The Journal of Nutrition, Vol. 145, No. 5, 2015, p. 945-953.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Common variants and haplotypes in the TF, TNF-a, and TMPRSS6 genes are associated with iron status in a female black South African population

AU - Gichohi-Wainaina, W.N.

AU - Boonstra, A.

AU - Swinkels, D.W.

AU - Zimmermann, M.B.

AU - Feskens, E.J.M.

AU - Towers, G.W.

PY - 2015

Y1 - 2015

N2 - 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 aimed to investigate associations of reported SNPs with iron markers in a South African cohort. Methods: Blood concentrations of hemoglobin, serum ferritin (SF), serum soluble transferrin receptor (sTfR), and body iron (BI) stores were determined from 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-a (TNF-a) and rs2071592 in nuclear factor ¿B 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-a, 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.

AB - 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 aimed to investigate associations of reported SNPs with iron markers in a South African cohort. Methods: Blood concentrations of hemoglobin, serum ferritin (SF), serum soluble transferrin receptor (sTfR), and body iron (BI) stores were determined from 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-a (TNF-a) and rs2071592 in nuclear factor ¿B 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-a, 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.

KW - tumor-necrosis-factor

KW - transferrin g277s mutation

KW - deficiency anemia

KW - serum hepcidin

KW - women

KW - risk

KW - disease

KW - hfe

KW - polymorphisms

KW - saturation

U2 - 10.3945/jn.114.209148

DO - 10.3945/jn.114.209148

M3 - Article

VL - 145

SP - 945

EP - 953

JO - The Journal of Nutrition

JF - The Journal of Nutrition

SN - 0022-3166

IS - 5

ER -