{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSaitohin (STH) is an intronless gene embedded within the human MAPT (tau) gene that encodes a 128–amino acid protein with a tissue‐expression pattern similar to tau. Initial discovery of STH reported its potential involvement in neurodegenerative diseases, with one study noting that a single nucleotide polymorphism (Q7R) in STH was over‐represented in late–onset Alzheimer’s disease subjects. Subsequent genetic analyses have explored STH as a candidate risk factor for several central nervous system disorders including Alzheimer’s disease, frontotemporal dementia, Parkinson’s disease, and even Huntington’s–like conditions, with some studies also extending its relevance to age–related macular degeneration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctional studies have begun to shed light on STH’s cellular role. Utilizing yeast two–hybrid screening, one report demonstrated that STH interacts in an allele–specific manner with peroxiredoxin 6, a bifunctional antioxidant enzyme whose levels increase in certain tauopathies. Additional experimental work found that STH can also bind to tau itself and to the non–receptor tyrosine kinase c–Abl, which phosphorylates STH—suggesting that STH may serve as a modulator of tau phosphorylation dynamics and oxidative stress responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe Q7R polymorphism (also referred to as rs62063857) remains the only recognized genetic variation in STH and has been extensively studied as a potential disease modifier. Numerous case–control and meta–analysis studies have evaluated whether the Q or R allele confers increased susceptibility or modifies phenotypic severity in neurodegenerative and neuropsychiatric disorders—including Alzheimer’s disease, frontotemporal dementia, Parkinson’s disease, and even schizophrenia—often in interaction with other risk factors such as APOE or COMT variants. Ethnic differences in allele frequency further complicate the picture, but the emerging consensus is that, although STH’s precise cellular function remains to be fully elucidated, its polymorphism appears to influence disease risk and cognitive outcomes in a variety of clinical contexts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "19"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chris Conrad, Cintia Vianna, Melissa Freeman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A polymorphic gene nested within an intron of the tau gene: implications for Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.112194599"}], "href": "https://doi.org/10.1073/pnas.112194599"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12032355"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12032355"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Patrice Verpillat, Sylvain Ricard, Didier Hannequin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Is the saitohin gene involved in neurodegenerative diseases?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Neurol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ana.10384"}], "href": "https://doi.org/10.1002/ana.10384"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12447938"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12447938"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Cezary Zekanowski, Beata Pepłońska, Maria Styczyńska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation screening of the MAPT and STH genes in Polish patients with clinically diagnosed frontotemporal dementia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dement Geriatr Cogn Disord (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000070999"}], "href": "https://doi.org/10.1159/000070999"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12826737"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12826737"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Onofre Combarros, Lucía Rodero, Jon Infante, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Age-dependent association between the Q7R polymorphism in the Saitohin gene and sporadic Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dement Geriatr Cogn Disord (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000071000"}], "href": "https://doi.org/10.1159/000071000"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12826738"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12826738"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Beata Pepłońska, Cezary Zekanowski, Dorota Religa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Strong association between Saitohin gene polymorphism and tau haplotype in the Polish population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Lett (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0304-3940(03)00788-2"}], "href": "https://doi.org/10.1016/s0304-3940(03"}, {"type": "t", "text": "00788-2) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12932819"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12932819"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "D Seripa, M G Matera, R P D'Andrea, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alzheimer disease risk associated with APOE4 is modified by STH gene polymorphism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/01.wnl.0000125693.59817.31"}], "href": "https://doi.org/10.1212/01.wnl.0000125693.59817.31"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15136700"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15136700"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Lei Gao, Sze-Wah Tse, Christopher Conrad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Saitohin, which is nested in the tau locus and confers allele-specific susceptibility to several neurodegenerative diseases, interacts with peroxiredoxin 6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M506116200"}], "href": "https://doi.org/10.1074/jbc.M506116200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16186110"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16186110"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yan Wang, Lei Gao, Christopher G Conrad, et al. 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