Associated Effect of <i>SLC40A1</i> and <i>TMPRSS6</i> Polymorphisms on Iron Overload
Mutations in the ferroportin (FPN) gene <i>SLC40A1</i> alter iron recycling and cause disturbances in iron homeostasis. The variants of <i>TMPRSS6</i> contribute to the development of iron deficiencies. In this study, we determined the role of FPN and <i>TMPRSS6</i&g...
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MDPI AG
2022-09-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/12/10/919 |
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| author | Lorena Duca Francesca Granata Elena Di Pierro Valentina Brancaleoni Giovanna Graziadei Isabella Nava |
| author_facet | Lorena Duca Francesca Granata Elena Di Pierro Valentina Brancaleoni Giovanna Graziadei Isabella Nava |
| author_sort | Lorena Duca |
| collection | DOAJ |
| description | Mutations in the ferroportin (FPN) gene <i>SLC40A1</i> alter iron recycling and cause disturbances in iron homeostasis. The variants of <i>TMPRSS6</i> contribute to the development of iron deficiencies. In this study, we determined the role of FPN and <i>TMPRSS6</i> gene polymorphisms in the modulation of iron homeostasis based on biochemical parameters. PCR analysis and sequencing were performed to determine the single nucleotide polymorphisms (SNPs) <i>SLC40A1</i> c.44–24G>C (rs1439816), <i>SLC40A1</i> c.663T>C (rs2304704), and <i>TMPRSS6</i> c.2207T>C (rs855791). Hemoglobin concentration and iron status were determined by standard procedures. We studied 79 iron-loaded individuals for <i>SLC40A1</i> polymorphisms. Interestingly, 35/79 individuals with <i>SLC40A1</i> SNPs also carried a <i>TMPRSS6</i> c.2207T>C polymorphism. The biochemical values of the iron overloaded individuals were compared to those of the individuals carrying <i>TMPRSS6</i> SNPs and the healthy individuals (wild-type group). The ferritin concentration, transferrin saturation % (TS%), and hemoglobin concentration were significantly higher in the participants with FPN SNPs than in the other three groups. The ferritin concentration and TS% were higher in participants with both <i>SLC40A1</i> and <i>TMPRSS6</i> SNPs than in the <i>TMPRSS6</i> and wild-type groups, while hemoglobin concentration was significantly higher than that in the <i>TMPRSS6</i> SNP group only. The participants with <i>TMPRSS6</i> SNPs had significantly lower ferritin concentration, TS%, and hemoglobin concentration than all the other groups. <i>SLC40A1</i> and <i>TMPRSS6</i> SNPs might act in the opposite direction, preventing the development of severe iron overload, and the modulation of the iron status by <i>TMPRSS6</i> SNPs might provide protection. |
| first_indexed | 2024-03-09T19:49:12Z |
| format | Article |
| id | doaj.art-630ba60cbe4e47e7b3cc42fd2d622d47 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T19:49:12Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-630ba60cbe4e47e7b3cc42fd2d622d472023-11-24T01:15:13ZengMDPI AGMetabolites2218-19892022-09-01121091910.3390/metabo12100919Associated Effect of <i>SLC40A1</i> and <i>TMPRSS6</i> Polymorphisms on Iron OverloadLorena Duca0Francesca Granata1Elena Di Pierro2Valentina Brancaleoni3Giovanna Graziadei4Isabella Nava5Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, U.O.C. Medicina Generale, 20122 Milano, ItalyFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, U.O.C. Medicina Generale, 20122 Milano, ItalyFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, U.O.C. Medicina Generale, 20122 Milano, ItalyFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, U.O.C. Medicina Generale, 20122 Milano, ItalyFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, U.O.C. Medicina Generale, 20122 Milano, ItalyFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, U.O.C. Medicina Generale, 20122 Milano, ItalyMutations in the ferroportin (FPN) gene <i>SLC40A1</i> alter iron recycling and cause disturbances in iron homeostasis. The variants of <i>TMPRSS6</i> contribute to the development of iron deficiencies. In this study, we determined the role of FPN and <i>TMPRSS6</i> gene polymorphisms in the modulation of iron homeostasis based on biochemical parameters. PCR analysis and sequencing were performed to determine the single nucleotide polymorphisms (SNPs) <i>SLC40A1</i> c.44–24G>C (rs1439816), <i>SLC40A1</i> c.663T>C (rs2304704), and <i>TMPRSS6</i> c.2207T>C (rs855791). Hemoglobin concentration and iron status were determined by standard procedures. We studied 79 iron-loaded individuals for <i>SLC40A1</i> polymorphisms. Interestingly, 35/79 individuals with <i>SLC40A1</i> SNPs also carried a <i>TMPRSS6</i> c.2207T>C polymorphism. The biochemical values of the iron overloaded individuals were compared to those of the individuals carrying <i>TMPRSS6</i> SNPs and the healthy individuals (wild-type group). The ferritin concentration, transferrin saturation % (TS%), and hemoglobin concentration were significantly higher in the participants with FPN SNPs than in the other three groups. The ferritin concentration and TS% were higher in participants with both <i>SLC40A1</i> and <i>TMPRSS6</i> SNPs than in the <i>TMPRSS6</i> and wild-type groups, while hemoglobin concentration was significantly higher than that in the <i>TMPRSS6</i> SNP group only. The participants with <i>TMPRSS6</i> SNPs had significantly lower ferritin concentration, TS%, and hemoglobin concentration than all the other groups. <i>SLC40A1</i> and <i>TMPRSS6</i> SNPs might act in the opposite direction, preventing the development of severe iron overload, and the modulation of the iron status by <i>TMPRSS6</i> SNPs might provide protection.https://www.mdpi.com/2218-1989/12/10/919<i>SLC40A1</i><i>TMPRSS6</i>ferroportinmatriptase-2ironiron overload |
| spellingShingle | Lorena Duca Francesca Granata Elena Di Pierro Valentina Brancaleoni Giovanna Graziadei Isabella Nava Associated Effect of <i>SLC40A1</i> and <i>TMPRSS6</i> Polymorphisms on Iron Overload Metabolites <i>SLC40A1</i> <i>TMPRSS6</i> ferroportin matriptase-2 iron iron overload |
| title | Associated Effect of <i>SLC40A1</i> and <i>TMPRSS6</i> Polymorphisms on Iron Overload |
| title_full | Associated Effect of <i>SLC40A1</i> and <i>TMPRSS6</i> Polymorphisms on Iron Overload |
| title_fullStr | Associated Effect of <i>SLC40A1</i> and <i>TMPRSS6</i> Polymorphisms on Iron Overload |
| title_full_unstemmed | Associated Effect of <i>SLC40A1</i> and <i>TMPRSS6</i> Polymorphisms on Iron Overload |
| title_short | Associated Effect of <i>SLC40A1</i> and <i>TMPRSS6</i> Polymorphisms on Iron Overload |
| title_sort | associated effect of i slc40a1 i and i tmprss6 i polymorphisms on iron overload |
| topic | <i>SLC40A1</i> <i>TMPRSS6</i> ferroportin matriptase-2 iron iron overload |
| url | https://www.mdpi.com/2218-1989/12/10/919 |
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