<i>MAPT</i> Subhaplotypes in Different Progressive Supranuclear Palsy Phenotypes
<b>Background:</b> Progressive Supranuclear Palsy (PSP) is a rare neurodegenerative disorder characterized by abnormal tau protein aggregation. The <i>MAPT</i> gene encodes for tau protein. The <i>MAPT</i> locus harbors two major haplotypes, H1 and H2, with H1 and...
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MDPI AG
2025-06-01
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| author | Monica Gagliardi Radha Procopio Alessia Felicetti Grazia Annesi Mariagrazia Talarico Basilio Vescio Aldo Quattrone Andrea Quattrone |
| author_facet | Monica Gagliardi Radha Procopio Alessia Felicetti Grazia Annesi Mariagrazia Talarico Basilio Vescio Aldo Quattrone Andrea Quattrone |
| author_sort | Monica Gagliardi |
| collection | DOAJ |
| description | <b>Background:</b> Progressive Supranuclear Palsy (PSP) is a rare neurodegenerative disorder characterized by abnormal tau protein aggregation. The <i>MAPT</i> gene encodes for tau protein. The <i>MAPT</i> locus harbors two major haplotypes, H1 and H2, with H1 and its subhaplotypes being associated with an increased risk of PSP. <b>Methods:</b> In this study, we genotyped rs8070723 in a cohort of 73 PSP patients, including 47 PSP Richardson Syndrome (PSP-RS) and 27 PSP variants (vPSP), and 93 age-matched healthy controls (HC) from Southern Italy. <b>Results:</b> Haplotype analysis identified H1 and H2 haplotypes that conferred a risk (OR, 2.620; 95% CI, 1.399–5.140; <i>p</i> = 0.0035) and a protective effect (OR, 0.370; 95% CI, 0.196–0.695; <i>p</i> = 0.0015), respectively. In addition, we genotyped five <i>MAPT</i> variants (rs1467967, rs242557, rs3785883, rs2471738, and rs7521) that, together with rs8070723, defined H1 subhaplotypes. We identified 18 distinct <i>MAPT</i> H1 subhaplotypes, among which H1j displayed a nominally significant reduced risk of PSP (OR, 0.201; 95% CI, 0.044–0.915; <i>p</i> = 0.0265). <b>Conclusions:</b> These findings reinforce the role of <i>MAPT</i> genetic variation in PSP pathogenesis and highlight the potential impact of haplotype diversity on disease susceptibility. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-06-01 |
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| series | Biomedicines |
| spelling | doaj-art-dd5ae68fe6604d6c8d189a3de737d2582025-08-20T03:27:22ZengMDPI AGBiomedicines2227-90592025-06-01136140510.3390/biomedicines13061405<i>MAPT</i> Subhaplotypes in Different Progressive Supranuclear Palsy PhenotypesMonica Gagliardi0Radha Procopio1Alessia Felicetti2Grazia Annesi3Mariagrazia Talarico4Basilio Vescio5Aldo Quattrone6Andrea Quattrone7Neuroscience Research Center, Magna Graecia University, 88100 Catanzaro, ItalyNeuroscience Research Center, Magna Graecia University, 88100 Catanzaro, ItalyInstitute of Neurology, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, ItalyInstitute for Biomedical Research and Innovation, National Research Council, 87050 Cosenza, ItalyStem Cell Laboratory, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, ItalyBiotecnomed S.c.a.r.l., 88100 Catanzaro, ItalyNeuroscience Research Center, Magna Graecia University, 88100 Catanzaro, ItalyNeuroscience Research Center, Magna Graecia University, 88100 Catanzaro, Italy<b>Background:</b> Progressive Supranuclear Palsy (PSP) is a rare neurodegenerative disorder characterized by abnormal tau protein aggregation. The <i>MAPT</i> gene encodes for tau protein. The <i>MAPT</i> locus harbors two major haplotypes, H1 and H2, with H1 and its subhaplotypes being associated with an increased risk of PSP. <b>Methods:</b> In this study, we genotyped rs8070723 in a cohort of 73 PSP patients, including 47 PSP Richardson Syndrome (PSP-RS) and 27 PSP variants (vPSP), and 93 age-matched healthy controls (HC) from Southern Italy. <b>Results:</b> Haplotype analysis identified H1 and H2 haplotypes that conferred a risk (OR, 2.620; 95% CI, 1.399–5.140; <i>p</i> = 0.0035) and a protective effect (OR, 0.370; 95% CI, 0.196–0.695; <i>p</i> = 0.0015), respectively. In addition, we genotyped five <i>MAPT</i> variants (rs1467967, rs242557, rs3785883, rs2471738, and rs7521) that, together with rs8070723, defined H1 subhaplotypes. We identified 18 distinct <i>MAPT</i> H1 subhaplotypes, among which H1j displayed a nominally significant reduced risk of PSP (OR, 0.201; 95% CI, 0.044–0.915; <i>p</i> = 0.0265). <b>Conclusions:</b> These findings reinforce the role of <i>MAPT</i> genetic variation in PSP pathogenesis and highlight the potential impact of haplotype diversity on disease susceptibility.https://www.mdpi.com/2227-9059/13/6/1405<i>MAPT</i> geneprogressive supranuclear palsyhaplotypes |
| spellingShingle | Monica Gagliardi Radha Procopio Alessia Felicetti Grazia Annesi Mariagrazia Talarico Basilio Vescio Aldo Quattrone Andrea Quattrone <i>MAPT</i> Subhaplotypes in Different Progressive Supranuclear Palsy Phenotypes Biomedicines <i>MAPT</i> gene progressive supranuclear palsy haplotypes |
| title | <i>MAPT</i> Subhaplotypes in Different Progressive Supranuclear Palsy Phenotypes |
| title_full | <i>MAPT</i> Subhaplotypes in Different Progressive Supranuclear Palsy Phenotypes |
| title_fullStr | <i>MAPT</i> Subhaplotypes in Different Progressive Supranuclear Palsy Phenotypes |
| title_full_unstemmed | <i>MAPT</i> Subhaplotypes in Different Progressive Supranuclear Palsy Phenotypes |
| title_short | <i>MAPT</i> Subhaplotypes in Different Progressive Supranuclear Palsy Phenotypes |
| title_sort | i mapt i subhaplotypes in different progressive supranuclear palsy phenotypes |
| topic | <i>MAPT</i> gene progressive supranuclear palsy haplotypes |
| url | https://www.mdpi.com/2227-9059/13/6/1405 |
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