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

Gichohi-Wainaina, Wanjiku N.; Melse‐Boonstra, Alida; Swinkels, Dorine W.; Zimmermann, Michael; Feskens, Edith J. M.; Towers, G. Wayne

doi:10.3945/jn.114.209148

Cited by 17 publications

(14 citation statements)

References 58 publications

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“…The Chinese Han population study by Gan et al and another study by Chamber et al, l which include SNP rs855791 and rs4820268 of the TMPRSS6 genes showed that minor allele frequency (MAF) of both SNPs in Asia was comparable with the finding in our study population (>55%) [5,14]. There is a considerable discrepancy in the minor allele frequency distribution of both SNPs among the Asian, African and European population [5,14,15]. The minor allele frequency of SNP rs855791 and rs4820268 tend to be lower in African than European and Asian populations.…”

Section: Discussionsupporting

confidence: 83%

The Association of TMPRSS6 Gene Polymorphism and Iron Intake with Iron Status among Under-Two-Year-Old Children in Lombok, Indonesia

et al. 2019

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Multiple common variants in transmembrane protease serine 6 (TMPRSS6) were associated with the plasma iron concentration in genome-wide association studies, but their effect in young children where anemia and iron deficiency (ID) were prevalent has not been reported, particularly taking account of iron intake. This study aims to investigate whether TMPRSS6 SNPs (rs855791 and rs4820268) and iron intake are associated with a low iron and hemoglobin concentration in under-two-year-old children. The study analyzed the baseline of a randomized trial (NUPICO, ClinicalTrials.gov NCT01504633) in East Lombok, Indonesia. Children aged 6–17 months (n = 121) were included in this study. The multiple linear regressions showed that TMPRSS6 decreased serum ferritin (SF) by 4.50 g/L per copy minor allele (A) of rs855791 (p = 0.08) and by 5.00 μg/L per copy minor allele (G) of rs4820268 (p = 0.044). There were no associations between rs855791 and rs4820268 with soluble transferrin receptor (sTfR) and hemoglobin (Hb) concentration (rs855791; p = 0.38 and p = 0.13, rs4820268; p = 0.17 and p = 0.33). The finding suggests the need for further studies to explore whether the nutrient recommendation for iron should be based on genetic characteristics, particularly for children who have mutation in TMPRSS6.

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Section: Discussionsupporting

confidence: 83%

The Association of TMPRSS6 Gene Polymorphism and Iron Intake with Iron Status among Under-Two-Year-Old Children in Lombok, Indonesia

et al. 2019

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“…In contrast, in our study, all participants had lived in the endemic area all their lives and the association was additive rather than recessive, furthermore the MAF in Courtin’s studies was 24%, whilst in ours it was 14%, suggesting significant differences in population structure between the two studies. Varying results in TNFA associations studies are not uncommon, multiple candidate gene association studies of TNFA- 308 (rs1800629) and malaria have found inconsistent results in different populations [ 25 , 26 ]. Another explanation could be that the TNFA- 308 has no effect but is in linkage disequilibrium (LD) with another unidentified polymorphism.…”

Section: Discussionmentioning

confidence: 99%

Candidate genes-based investigation of susceptibility to Human African Trypanosomiasis in Côte d’Ivoire

et al. 2017

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Human African Trypanosomiasis (HAT) or sleeping sickness is a Neglected Tropical Disease. Long regarded as an invariably fatal disease, there is increasing evidence that infection by T. b. gambiense can result in a wide range of clinical outcomes, including latent infections, which are long lasting infections with no parasites detectable by microscopy. The determinants of this clinical diversity are not well understood but could be due in part to parasite or host genetic diversity in multiple genes, or their interactions. A candidate gene association study was conducted in Côte d’Ivoire using a case-control design which included a total of 233 subjects (100 active HAT cases, 100 controls and 33 latent infections). All three possible pairwise comparisons between the three phenotypes were tested using 96 SNPs in16 candidate genes (IL1, IL4, IL4R, IL6, IL8, IL10, IL12, IL12R, TNFA, INFG, MIF, APOL1, HPR, CFH, HLA-A and HLA-G). Data from 77 SNPs passed quality control. There were suggestive associations at three loci in IL6 and TNFA in the comparison between active cases and controls, one SNP in each of APOL1, MIF and IL6 in the comparison between latent infections and active cases and seven SNP in IL4, HLA-G and TNFA between latent infections and controls. No associations remained significant after Bonferroni correction, but the Benjamini Hochberg false discovery rate test indicated that there were strong probabilities that at least some of the associations were genuine. The excess of associations with latent infections despite the small number of samples available suggests that these subjects form a distinct genetic cluster different from active HAT cases and controls, although no clustering by phenotype was observed by principle component analysis. This underlines the complexity of the interactions existing between host genetic polymorphisms and parasite diversity.

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“…The majority of the studies (59/64) were conducted in Europe, Asia and the USA (Fig 1, S2 Table). Only five studies were conducted in Africa, two in Rwanda [49,50], one in Zimbabwe [51], one in South Africa [52] and one meta-analysis across Kenya, Tanzania and South Africa [30]. Across the 64 studies, 50 SNPs were identified in six genes (TMPRSS6, HAMP, TF, TFR2, SLC40A1 and HFE) (S1 Table).…”

Section: Genetic Variants Associated With Iron Imbalancesmentioning

confidence: 99%

Differences in the frequency of genetic variants associated with iron imbalance among global populations

et al. 2020

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Iron deficiency anaemia is a major health problem affecting approximately 1.2 billion people worldwide. Young children, women of reproductive age and pregnant women living in sub-Saharan Africa are the most vulnerable. It is estimated that iron deficiency accounts for half of anaemia cases. Apart from nutritional deficiency, infection, inflammation and genetic factors are the major drivers of anaemia. However, the role of genetic risk factors has not been thoroughly investigated. This is particularly relevant in African populations, as they carry high genetic diversity and have a high prevalence of anaemia. Multiple genetic variations in iron regulatory genes have been linked to impaired iron status. Here we conducted a literature review to identify genetic variants associated with iron imbalance among global populations. We compare their allele frequencies and risk scores and we investigated populationspecific selection among populations of varying geographic origin using data from the Keneba Biobank representing individuals in rural Gambia and the 1000 Genomes Project. We identified a significant lack of data on the genetic determinants of iron status in sub-Saharan Africa. Most of the studies on genetic determinants of iron status have been conducted in Europeans. Also, we identified population differences in allele frequencies in candidate putative genetic risk factors. Given the disproportionately high genetic diversity in African populations coupled with their high prevalence of iron deficiency, there is need to investigate the genetic influences of low iron status in Sub-Saharan Africa. The resulting insights may inform the future implementation of iron intervention strategies.

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

Cited by 17 publications

References 58 publications

The Association of TMPRSS6 Gene Polymorphism and Iron Intake with Iron Status among Under-Two-Year-Old Children in Lombok, Indonesia

The Association of TMPRSS6 Gene Polymorphism and Iron Intake with Iron Status among Under-Two-Year-Old Children in Lombok, Indonesia

Candidate genes-based investigation of susceptibility to Human African Trypanosomiasis in Côte d’Ivoire

Differences in the frequency of genetic variants associated with iron imbalance among global populations

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