{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T11:28:14Z","timestamp":1791026894760,"version":"4.1.0"},"reference-count":20,"publisher":"BMJ","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2001,4,3]]},"published-print":{"date-parts":[[2001,6,1]]},"abstract":"<jats:p>Mutations in the presenilin 1 gene (<jats:italic>PS1<\/jats:italic>) account for the majority of early onset, familial, autosomal dominant forms of Alzheimer's disease (AD), whereas its role in other late onset forms of AD remains unclear. A \u221248 C\/T polymorphism in the <jats:italic>PS1<\/jats:italic> promoter has been associated with an increased genetic risk in early onset complex AD and moreover has been shown to influence the expression of the <jats:italic>PS1<\/jats:italic> gene. This raises the possibility that previous conflicting findings from association studies with homozygosity for the <jats:italic>PS1<\/jats:italic> intron 8 polymorphism might be the result of linkage disequilibrium with the \u201348 CC genotype. Here we provide further evidence of increased risk of AD associated with homozygosity for the \u221248 CC genotype (odds ratio=1.6). We also report a phenotypic correlation with A\u03b2<jats:sub>40<\/jats:sub>, A\u03b2<jats:sub>42(43)<\/jats:sub>, and total A\u03b2 load in AD brains. The \u221248 CC genotype was associated with 47% greater total A\u03b2 load (p&lt;0.003) compared to CT + TT genotype bearers. These results suggest that the \u201348 C\/T polymorphism in the<jats:italic>PS1<\/jats:italic> promoter may increase the risk of AD, perhaps by altering <jats:italic>PS1<\/jats:italic> gene expression and thereby influencing A\u03b2 load.<\/jats:p>","DOI":"10.1136\/jmg.38.6.353","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T06:38:40Z","timestamp":1027751920000},"page":"353-355","source":"Crossref","is-referenced-by-count":46,"title":["The \u221248 C\/T polymorphism in the presenilin 1 promoter is associated with an increased risk of developing Alzheimer's disease and an increased A\u03b2 load in brain"],"prefix":"10.1136","volume":"38","author":[{"given":"Jean-Charles","family":"Lambert","sequence":"first","affiliation":[{"name":"aMolecular Psychiatry Department, Division of Neuroscience, Queen Elizabeth Psychiatry Hospital, University of Birmingham, Birmingham B15 2QZ, UK, \n\nbLaboratory Medicine Academic Group, Department of Medicine, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK, \n\ncINSERM 508, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP 245, 59019 Lille C\u00e9dex, France, \n\ndDepartment of Mental Health, Foresterhill, University of Aberdeen, Aberdeen AB25 2ZD, UK, \n\neDepartment of N"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M A","family":"Mann","sequence":"additional","affiliation":[{"name":"aMolecular Psychiatry Department, Division of Neuroscience, Queen Elizabeth Psychiatry Hospital, University of Birmingham, Birmingham B15 2QZ, UK, \n\nbLaboratory Medicine Academic Group, Department of Medicine, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK, \n\ncINSERM 508, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP 245, 59019 Lille C\u00e9dex, France, \n\ndDepartment of Mental Health, Foresterhill, University of Aberdeen, Aberdeen AB25 2ZD, UK, \n\neDepartment of N"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith M","family":"Harris","sequence":"additional","affiliation":[{"name":"aMolecular Psychiatry Department, Division of Neuroscience, Queen Elizabeth Psychiatry Hospital, University of Birmingham, Birmingham B15 2QZ, UK, \n\nbLaboratory Medicine Academic Group, Department of Medicine, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK, \n\ncINSERM 508, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP 245, 59019 Lille C\u00e9dex, France, \n\ndDepartment of Mental Health, Foresterhill, University of Aberdeen, Aberdeen AB25 2ZD, UK, \n\neDepartment of N"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Christine","family":"Chartier-Harlin","sequence":"additional","affiliation":[{"name":"aMolecular Psychiatry Department, Division of Neuroscience, Queen Elizabeth Psychiatry Hospital, University of Birmingham, Birmingham B15 2QZ, UK, \n\nbLaboratory Medicine Academic Group, Department of Medicine, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK, \n\ncINSERM 508, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP 245, 59019 Lille C\u00e9dex, France, \n\ndDepartment of Mental Health, Foresterhill, University of Aberdeen, Aberdeen AB25 2ZD, UK, \n\neDepartment of N"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair","family":"Cumming","sequence":"additional","affiliation":[{"name":"aMolecular Psychiatry Department, Division of Neuroscience, Queen Elizabeth Psychiatry Hospital, University of Birmingham, Birmingham B15 2QZ, UK, \n\nbLaboratory Medicine Academic Group, Department of Medicine, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK, \n\ncINSERM 508, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP 245, 59019 Lille C\u00e9dex, France, \n\ndDepartment of Mental Health, Foresterhill, University of Aberdeen, Aberdeen AB25 2ZD, UK, \n\neDepartment of N"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Coates","sequence":"additional","affiliation":[{"name":"aMolecular Psychiatry Department, Division of Neuroscience, Queen Elizabeth Psychiatry Hospital, University of Birmingham, Birmingham B15 2QZ, UK, \n\nbLaboratory Medicine Academic Group, Department of Medicine, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK, \n\ncINSERM 508, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP 245, 59019 Lille C\u00e9dex, France, \n\ndDepartment of Mental Health, Foresterhill, University of Aberdeen, Aberdeen AB25 2ZD, UK, \n\neDepartment of N"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Lemmon","sequence":"additional","affiliation":[{"name":"aMolecular Psychiatry Department, Division of Neuroscience, Queen Elizabeth Psychiatry Hospital, University of Birmingham, Birmingham B15 2QZ, UK, \n\nbLaboratory Medicine Academic 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