The SIRT2 polymorphism rs10410544 and risk of Alzheimer's disease in two Caucasian case–control cohorts

Medientyp: E-Artikel
Titel: The SIRT2 polymorphism rs10410544 and risk of Alzheimer's disease in two Caucasian case–control cohorts
Beteiligte: Polito, Letizia; Kehoe, Patrick G.; Davin, Annalisa; Benussi, Luisa; Ghidoni, Roberta; Binetti, Giuliano; Quadri, Pierluigi; Lucca, Ugo; Tettamanti, Mauro; Clerici, Francesca; Bagnoli, Silvia; Galimberti, Daniela; Nacmias, Benedetta; Sorbi, Sandro; Guaita, Antonio; Scarpini, Elio; Mariani, Claudio; Forloni, Gianluigi; Albani, Diego
Erschienen: Wiley, 2013
Erschienen in: Alzheimer's & Dementia
Sprache: Englisch
DOI: 10.1016/j.jalz.2012.02.003
ISSN: 1552-5260; 1552-5279
Schlagwörter: Psychiatry and Mental health ; Cellular and Molecular Neuroscience ; Geriatrics and Gerontology ; Neurology (clinical) ; Developmental Neuroscience ; Health Policy ; Epidemiology
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Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Human sirtuins are a current hotspot for research in neurodegenerative disorders, including Alzheimer's disease (AD). This study investigated whether genetic variants in two members of the sirtuin family, <jats:italic>SIRT2</jats:italic> and <jats:italic>SIRT3</jats:italic>, affected AD susceptibility.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A genetic case–control study was performed, comprising 534 probable AD cases and 638 nondemented control subjects from the north of Italy and Canton Ticino, Switzerland (discovery population). The study was focused on <jats:italic>SIRT2</jats:italic> rs10410544, <jats:italic>SIRT3</jats:italic> rs4980329, and <jats:italic>SIRT3</jats:italic> rs536715 single nucleotide polymorphisms (SNPs). These SNPs were genotyped by real‐time polymerase chain reaction allelic discrimination assay or restriction fragment length polymorphism. The SNPs rs7412 and rs429358, mapping within the apolipoprotein E (<jats:italic>APOE</jats:italic>) gene, were genotyped by real‐time polymerase chain reaction allelic discrimination assay too. In a replication population comprising 756 AD cases and 847 nondemented control subjects, <jats:italic>SIRT2</jats:italic> rs10410544, <jats:italic>APOE</jats:italic> rs7412, and <jats:italic>APOE</jats:italic> rs429358 were genotyped as mentioned previously.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In the discovery population, we observed an association between <jats:italic>SIRT2</jats:italic> rs10410544 T allele and AD (adjusted odds ratio [OR] = 1.23, 95% confidence interval [CI]: 1.02–1.50, <jats:italic>P</jats:italic> = .02, after correction for sex, age, and <jats:italic>APOE ɛ4</jats:italic> genotype). The association between AD and <jats:italic>SIRT2</jats:italic> rs10410544 T allele was only present in <jats:italic>APOE</jats:italic> ɛ4 noncarriers (adjusted OR = 1.29, 95% CI: 1.03–1.61, <jats:italic>P</jats:italic> = .03). The replication study did not confirm this evidence. However, the combined analysis on the two cohorts detected the association (adjusted OR = 1.17, 95% CI: 1.02–1.35, <jats:italic>P</jats:italic> = .02), and only <jats:italic>APOE</jats:italic> ɛ4 noncarriers were at risk (adjusted OR = 1.2, 95% CI: 1.02–1.43, <jats:italic>P</jats:italic> = .03).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The <jats:italic>SIRT2</jats:italic> rs10410544 T allele deserves further investigation as a novel minor genetic risk factor for AD in the <jats:italic>APOE</jats:italic> ɛ4‐negative Caucasian population.</jats:p></jats:sec>

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