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We sought to investigate the effects of common\u00a0<jats:italic>TMPRSS6<\/jats:italic>\u00a0and\u00a0<jats:italic>TF<\/jats:italic>\u00a0gene SNPs on iron status indicators in a cohort of healthy Africans from rural Gambia. We measured iron biomarkers and haematology traits on individuals participating in the Keneba Biobank with genotype data on\u00a0<jats:italic>TMPRSS6<\/jats:italic>\u00a0(rs2235321, rs855791, rs4820268, rs2235324, rs2413450 and rs5756506) and\u00a0<jats:italic>TF<\/jats:italic>\u00a0(rs3811647 and rs1799852), n\u2009=\u20091316. After controlling for inflammation, age and sex, we analysed the effects of carrying either single or multiple iron-lowering alleles on iron status. <jats:italic>TMPRSS6<\/jats:italic> rs2235321 significantly affected plasma hepcidin concentrations (AA genotypes having lower hepcidin levels; F ratio 3.7, P\u2009=\u20090.014) with greater impact in individuals with low haemoglobin or ferritin. No other\u00a0<jats:italic>TMPRSS6<\/jats:italic>\u00a0variant affected hepcidin. None of the\u00a0<jats:italic>TMPRSS6<\/jats:italic>\u00a0variants nor a\u00a0<jats:italic>TMPRSS6<\/jats:italic>\u00a0allele risk score affected other iron biomarkers or haematological traits.\u00a0<jats:italic>TF<\/jats:italic>\u00a0rs3811647 AA carriers had 21% higher transferrin (F ratio 16.0, P\u2009&lt;\u20090.0001), 24% higher unsaturated iron-binding capacity (F ratio 12.8, P\u2009&lt;\u20090.0001) and 25% lower transferrin saturation (F ratio 4.3, P\u2009&lt;\u20090.0001) compared to GG carriers. <jats:italic>TF<\/jats:italic>\u00a0rs3811647 was strongly associated with transferrin, unsaturated iron-binding capacity (UIBC) and transferrin saturation (TSAT) with a single allele effect of 8\u201312%. There was no association between either\u00a0<jats:italic>TF<\/jats:italic>\u00a0SNP and any haematological traits or iron biomarkers. We identified meaningful associations between\u00a0<jats:italic>TMPRSS6<\/jats:italic>\u00a0rs2235321 and hepcidin and\u00a0replicated the previous findings on the effects of <jats:italic>TF<\/jats:italic>\u00a0rs3811647 on transferrin and iron binding capacity. However, the effects are subtle and contribute little to population variance. Further genetic and functional studies, including polymorphisms frequent in Africa populations, are needed to identify markers for genetically stratified approaches to prevention or treatment of iron deficiency anaemia.<\/jats:p>","DOI":"10.1038\/s41598-021-87565-5","type":"journal-article","created":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T10:05:57Z","timestamp":1618308357000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Association of common\u00a0TMPRSS6 and TF gene variants with hepcidin and iron status in healthy rural Gambians"],"prefix":"10.1038","volume":"11","author":[{"given":"Momodou W.","family":"Jallow","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana","family":"Campino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew M.","family":"Prentice","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Cerami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,4,13]]},"reference":[{"issue":"4","key":"87565_CR1","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1152\/physrev.00008.2013","volume":"93","author":"T Ganz","year":"2013","unstructured":"Ganz, T. Systemic iron homeostasis. Physiol. Rev. 93(4), 1721\u20131741 (2013).","journal-title":"Physiol. Rev."},{"issue":"10","key":"87565_CR2","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1182\/blood-2013-07-515957","volume":"123","author":"K Mleczko-Sanecka","year":"2014","unstructured":"Mleczko-Sanecka, K. et al. Unbiased RNAi screen for hepcidin regulators links hepcidin suppression to proliferative Ras\/RAF and nutrient-dependent mTOR signaling. Blood 123(10), 1574\u20131585 (2014).","journal-title":"Blood"},{"issue":"11","key":"87565_CR3","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1038\/ng.456","volume":"41","author":"B Benyamin","year":"2009","unstructured":"Benyamin, B. et al. Common variants in TMPRSS6 are associated with iron status and erythrocyte volume. Nat. Genet. 41(11), 1173\u20131175 (2009).","journal-title":"Nat. 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