Association of common TMPRSS6 and TF gene variants with hepcidin and iron status in healthy rural Gambians

Abstract Genome-wide association studies in Europeans and Asians have identified numerous variants in the transmembrane protease serine 6 (TMPRSS6) and transferrin (TF) genes that are associated with changes in iron status. We sought to investigate the effects of common TMPRSS6 and TF gene SNPs on i...

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Autores principales:	Momodou W. Jallow, Susana Campino, Andrew M. Prentice, Carla Cerami
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4f5d466afd1243188432805331e09794
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spelling	oai:doaj.org-article:4f5d466afd1243188432805331e097942021-12-02T14:27:56ZAssociation of common TMPRSS6 and TF gene variants with hepcidin and iron status in healthy rural Gambians10.1038/s41598-021-87565-52045-2322https://doaj.org/article/4f5d466afd1243188432805331e097942021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87565-5https://doaj.org/toc/2045-2322Abstract Genome-wide association studies in Europeans and Asians have identified numerous variants in the transmembrane protease serine 6 (TMPRSS6) and transferrin (TF) genes that are associated with changes in iron status. We sought to investigate the effects of common TMPRSS6 and TF gene 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 TMPRSS6 (rs2235321, rs855791, rs4820268, rs2235324, rs2413450 and rs5756506) and TF (rs3811647 and rs1799852), n = 1316. After controlling for inflammation, age and sex, we analysed the effects of carrying either single or multiple iron-lowering alleles on iron status. TMPRSS6 rs2235321 significantly affected plasma hepcidin concentrations (AA genotypes having lower hepcidin levels; F ratio 3.7, P = 0.014) with greater impact in individuals with low haemoglobin or ferritin. No other TMPRSS6 variant affected hepcidin. None of the TMPRSS6 variants nor a TMPRSS6 allele risk score affected other iron biomarkers or haematological traits. TF rs3811647 AA carriers had 21% higher transferrin (F ratio 16.0, P < 0.0001), 24% higher unsaturated iron-binding capacity (F ratio 12.8, P < 0.0001) and 25% lower transferrin saturation (F ratio 4.3, P < 0.0001) compared to GG carriers. TF rs3811647 was strongly associated with transferrin, unsaturated iron-binding capacity (UIBC) and transferrin saturation (TSAT) with a single allele effect of 8–12%. There was no association between either TF SNP and any haematological traits or iron biomarkers. We identified meaningful associations between TMPRSS6 rs2235321 and hepcidin and replicated the previous findings on the effects of TF rs3811647 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.Momodou W. JallowSusana CampinoAndrew M. PrenticeCarla CeramiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Momodou W. Jallow Susana Campino Andrew M. Prentice Carla Cerami Association of common TMPRSS6 and TF gene variants with hepcidin and iron status in healthy rural Gambians
description	Abstract Genome-wide association studies in Europeans and Asians have identified numerous variants in the transmembrane protease serine 6 (TMPRSS6) and transferrin (TF) genes that are associated with changes in iron status. We sought to investigate the effects of common TMPRSS6 and TF gene 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 TMPRSS6 (rs2235321, rs855791, rs4820268, rs2235324, rs2413450 and rs5756506) and TF (rs3811647 and rs1799852), n = 1316. After controlling for inflammation, age and sex, we analysed the effects of carrying either single or multiple iron-lowering alleles on iron status. TMPRSS6 rs2235321 significantly affected plasma hepcidin concentrations (AA genotypes having lower hepcidin levels; F ratio 3.7, P = 0.014) with greater impact in individuals with low haemoglobin or ferritin. No other TMPRSS6 variant affected hepcidin. None of the TMPRSS6 variants nor a TMPRSS6 allele risk score affected other iron biomarkers or haematological traits. TF rs3811647 AA carriers had 21% higher transferrin (F ratio 16.0, P < 0.0001), 24% higher unsaturated iron-binding capacity (F ratio 12.8, P < 0.0001) and 25% lower transferrin saturation (F ratio 4.3, P < 0.0001) compared to GG carriers. TF rs3811647 was strongly associated with transferrin, unsaturated iron-binding capacity (UIBC) and transferrin saturation (TSAT) with a single allele effect of 8–12%. There was no association between either TF SNP and any haematological traits or iron biomarkers. We identified meaningful associations between TMPRSS6 rs2235321 and hepcidin and replicated the previous findings on the effects of TF rs3811647 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.
format	article
author	Momodou W. Jallow Susana Campino Andrew M. Prentice Carla Cerami
author_facet	Momodou W. Jallow Susana Campino Andrew M. Prentice Carla Cerami
author_sort	Momodou W. Jallow
title	Association of common TMPRSS6 and TF gene variants with hepcidin and iron status in healthy rural Gambians
title_short	Association of common TMPRSS6 and TF gene variants with hepcidin and iron status in healthy rural Gambians
title_full	Association of common TMPRSS6 and TF gene variants with hepcidin and iron status in healthy rural Gambians
title_fullStr	Association of common TMPRSS6 and TF gene variants with hepcidin and iron status in healthy rural Gambians
title_full_unstemmed	Association of common TMPRSS6 and TF gene variants with hepcidin and iron status in healthy rural Gambians
title_sort	association of common tmprss6 and tf gene variants with hepcidin and iron status in healthy rural gambians
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4f5d466afd1243188432805331e09794
work_keys_str_mv	AT momodouwjallow associationofcommontmprss6andtfgenevariantswithhepcidinandironstatusinhealthyruralgambians AT susanacampino associationofcommontmprss6andtfgenevariantswithhepcidinandironstatusinhealthyruralgambians AT andrewmprentice associationofcommontmprss6andtfgenevariantswithhepcidinandironstatusinhealthyruralgambians AT carlacerami associationofcommontmprss6andtfgenevariantswithhepcidinandironstatusinhealthyruralgambians
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Association of common TMPRSS6 and TF gene variants with hepcidin and iron status in healthy rural Gambians

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