Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

Unravelling the genetics of iron status in African populations: candidate gene association studies.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Additional Information
    • Author(s):
    • Address:
      Wageningen University, Wageningen, Netherlands.
    • Publication Information:
      Netherlands
    • Abstract:
      Background: Investigating the manner in which genetic and environmental factors interact to increase susceptibility to iron deficiency, has the potential to impact on strategies to overcome iron deficiency as well as the development of biomarkers to monitor iron status in populations. Single nucleotide polymorphisms or genetic variants that may affect the composition and hence the functionality of proteins involved in iron metabolism have been the subject of recent genetic association studies. However, these investigations have not yet been carried out in African populations that differ genetically from populations of European ancestry and which bear the highest burden of iron deficiency. The overall aim of this thesis was to investigate the genetics of iron status in African populations using a candidate gene approach. Methods: In order to evaluate the association between identified TMPRSS6 gene variants and iron status we conducted a systematic review with meta-analyses. To investigate whether previously identified associations in populations of European ancestry are replicated in populations of African ancestry, we conducted candidate gene association studies. Twenty iron status-associated variants in 628 Kenyans, 609 Tanzanians, 608 South Africans and 228 African Americans were genotyped and associations investigated using haemoglobin and serum ferritin as outcome measures. Results: In our systematic review we included eleven studies on Caucasian populations, four on Asian populations and one study on an African-American population. Differences in minor allele frequencies (MAF) of 8 TMPRSS6 SNPs (rs855791, rs4820268, rs2111833, rs1421312, rs228921, rs228918, rs228919 and rs575620) across ethnic groups were observed; with the MAF of rs855791 being significantly higher in Asian populations than in Caucasians (0.55 vs 0.42). In the meta-analysis, the A allele of rs855791 was associated with lower haemoglobin and ferritin concentrations in all populations. This allele was also associated with increased serum transferrin receptor and transferrin concentrations. We observed similar associations for the G allele in rs4820268. In general, minor allele frequencies (MAF) from females in the PURE population were lower compared to those of males and females of European ancestry populations in the 1000 Genomes Project. In the TF gene, the SNP rs1799852 was associated with decreased serum ferritin (p=0.01) and body iron concentrations (p=0.03) and increased serum transferrin receptor (sTfR) concentrations (P=0.004), while rs3811647 was associated with transferrin receptor and body iron (both P=0.03) in a U-shaped manner. The chromosome 6 SNP allele combination (AAA) consisting of rs1799964 and rs1800629 both in TNF α and rs2071592 in NFKBIL1 was associated with higher odds for low serum ferritin concentrations (serum ferritin <15 µg/L; OR: 1.86 (95%-CI, 1.23-2.79)). The chromosome 22 SNP allele combination (GG) consisting of rs228918 and rs228921 in the TMPRSS6 gene was associated with lower odds for increased sTfR concentrations (sTfR >8.3 mg/L; OR: 0.79 (95%-CI, 0.63-0.98)). We successfully replicated reported significant associations with lowered haemoglobin concentrations for two loci in TMPRSS6 namely rs2413450 and rs4820268 and with increased haemoglobin concentrations for one locus in TF (rs3811658) when analysing the four populations of African ancestry. When ferritin was considered as an outcome measure, we replicated associations with increased ferritin concentrations in two loci namely, rs228918 in TMPRSS6 and rs1525892 in TF. No other significant associations were determined. Malaria rates were higher in Tanzanian children with the TNF_1031CC genotype (rs1799964) compared to the AA genotype (crude hazard ratio (HR), 95%CI: 1.41 [1.01-1.97], adjusted HR 1.31 [0.97-1.76]y) but were lower in those with the TNF_308AA genotype (rs1800629) (adjusted HR 0.13 [0.02-0.63]) compared to those harbouring the wild type homozygous genotype.
    • Number of References:
      many ref.
    • Subject Terms:
      Tropical Diseases;Human Nutrition;Protozoology
    • Subject Terms:
    • Accession Number:
      cachectin, cachexin, ethnic differences, genetic variability, genotypic variability, genotypic variation, hemoglobin, microelements, nutritional genomics, nutritional status, parasitic diseases, parasitic infestations, parasitosis, protozoal diseases, Tanganyika, tumor necrosis factor
    • CABICODES:
      Human Genetics and Molecular Medicine (VV080) (New June 2002)
      Physiology of Human Nutrition (VV120)
      Nutrition Related Disorders and Therapeutic Nutrition (VV130)
      Protozoan, Helminth and Arthropod Parasites of Humans (VV220) (New March 2000)
      General Molecular Biology (ZZ360) (Discontinued March 2000)
    • Accession Number:
      9007-73-2; 7439-89-6; 11096-37-0; 308079-78-9
    • Publication Information:
      Thesis; ISBN:9789462572102
    • Accession Number:
      20153142878
    • Copyright:
      ©2015 CAB International
  • Citations
    • ABNT:
      GICHOHI-WAINAINA, W. N. Unravelling the genetics of iron status in African populations: candidate gene association studies. 2015. Wageningen Universiteit (Wageningen University), Wageningen; Netherlands, 2015. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=lhh&AN=20153142878. Acesso em: 27 set. 2020.
    • AMA:
      Gichohi-Wainaina WN. Unravelling the genetics of iron status in African populations: candidate gene association studies. Unravelling the genetics of iron status in African populations: candidate gene association studies. 2015:198. Accessed September 27, 2020. http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=lhh&AN=20153142878
    • APA:
      Gichohi-Wainaina, W. N. (2015). Unravelling the genetics of iron status in African populations: candidate gene association studies [Wageningen Universiteit (Wageningen University)]. In Unravelling the genetics of iron status in African populations: candidate gene association studies (p. 198).
    • Chicago/Turabian: Author-Date:
      Gichohi-Wainaina, W. N. 2015. “Unravelling the Genetics of Iron Status in African Populations: Candidate Gene Association Studies.” Unravelling the Genetics of Iron Status in African Populations: Candidate Gene Association Studies. Wageningen; Netherlands: Wageningen Universiteit (Wageningen University). http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=lhh&AN=20153142878.
    • Harvard:
      Gichohi-Wainaina, W. N. (2015) Unravelling the genetics of iron status in African populations: candidate gene association studies, Unravelling the genetics of iron status in African populations: candidate gene association studies. Wageningen Universiteit (Wageningen University). Available at: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=lhh&AN=20153142878 (Accessed: 27 September 2020).
    • Harvard: Australian:
      Gichohi-Wainaina, WN 2015, ‘Unravelling the genetics of iron status in African populations: candidate gene association studies’, Wageningen Universiteit (Wageningen University), Wageningen; Netherlands, Unravelling the genetics of iron status in African populations: candidate gene association studies, p. 198, viewed 27 September 2020, .
    • MLA:
      Gichohi-Wainaina, W. N. “Unravelling the Genetics of Iron Status in African Populations: Candidate Gene Association Studies.” Unravelling the Genetics of Iron Status in African Populations: Candidate Gene Association Studies, Wageningen Universiteit (Wageningen University), 2015, p. 198. EBSCOhost, search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=lhh&AN=20153142878.
    • Chicago/Turabian: Humanities:
      Gichohi-Wainaina, W. N. “Unravelling the Genetics of Iron Status in African Populations: Candidate Gene Association Studies.” Unravelling the Genetics of Iron Status in African Populations: Candidate Gene Association Studies. Wageningen Universiteit (Wageningen University), 2015. http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=lhh&AN=20153142878.
    • Vancouver/ICMJE:
      Gichohi-Wainaina WN. Unravelling the genetics of iron status in African populations: candidate gene association studies [Internet]. Unravelling the genetics of iron status in African populations: candidate gene association studies. [Wageningen; Netherlands]: Wageningen Universiteit (Wageningen University); 2015 [cited 2020 Sep 27]. p. 198. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=lhh&AN=20153142878