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Titolo:
D10S1423 identifies a susceptibility locus for Alzheimer's disease in a prospective, longitudinal, double-blind study of asymptomatic individuals
Autore:
Zubenko, GS; Hughes, HB; Stiffler, JS;
Indirizzi:
Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA Univ Pittsburgh Pittsburgh PA USA 15213 sychiat, Pittsburgh, PA 15213 USA Carnegie Mellon Univ, Mellon Coll Sci, Dept Biol Sci, Pittsburgh, PA 15213USA Carnegie Mellon Univ Pittsburgh PA USA 15213 Sci, Pittsburgh, PA 15213USA
Titolo Testata:
MOLECULAR PSYCHIATRY
fascicolo: 4, volume: 6, anno: 2001,
pagine: 413 - 419
SICI:
1359-4184(200107)6:4<413:DIASLF>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMYLOID PRECURSOR PROTEIN; HIGH-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-E; MISSENSE MUTATIONS; LINKAGE ANALYSIS; GENOME SCAN; DEMENTIA; GENE; RISK; SCHIZOPHRENIA;
Keywords:
Alzheimer's disease; genetics; D10S1423; prospective, longitudinal study; asymptomatic individuals;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
62
Recensione:
Indirizzi per estratti:
Indirizzo: Zubenko, GS Western Psychiat Inst & Clin, E 1230,3811 OHara St, Pittsburgh, PA 15213 USA Western Psychiat Inst & Clin E 1230,3811 OHara St PittsburghPA USA 15213
Citazione:
G.S. Zubenko et al., "D10S1423 identifies a susceptibility locus for Alzheimer's disease in a prospective, longitudinal, double-blind study of asymptomatic individuals", MOL PSYCHI, 6(4), 2001, pp. 413-419

Abstract

Typical, later-onset forms of Alzheimer's disease (AD) appear to be influenced by multiple susceptibility loci, combinations of which contribute to the development of this disorder. We previously reported the results of a systematic survey of the human genome for the identification of highly informative DNA polymorphisms (SSTRPs) that target new AD risk genes. In additionto the APOE locus, our survey detected five new candidate susceptibility loci for AD, including D10S1423. An association of the D10S1423 234-bp allele with AD has been reported in three independent samples of AD cases and controls (Boston, Pittsburgh, Bonn). Data from our case-control studies suggest a strong synergistic interaction between the D10S1423 234-bp and APOE E4risk alleles (234-bp carrier: OR = 2.5, 95% CI = 1.4-4.5; E4 carrier: OR =8.3, 95% CI = 4.3-15.8; both alleles: OR = 23.1, 95% CI = 5.3-99.5). This report describes the prospective, longitudinal, double-blind assessment of the age-specific risk of AD encountered by 325 asymptomatic first-degree relatives of AD probands who carried the D10S1423 234-bp allele, the APOE E4 allele, or both, after 11.5 years of systematic follow-up. A total of 18 incident cases of AD were detected during the first 3379 subject-years of this longitudinal study. The effects of carrying either or both of the D10S1423 234-bp and APOE E4 alleles on the age-specific risk of developing AD weredetermined using Kaplan-Meier survival analysis. The age-specific risk of developing AD was the greatest for individuals who carried both alleles (Mantel-Cox statistic = 20.12, df = 3, P = 0.0002; Breslow statistic = 13.36, df = 3, P = 0.004). Cox proportional hazards models were developed to estimate the risk ratios for each genotype, controlling for the potential effects of age at recruitment, sex, and years of education. In the resulting bestfitting model, only individuals who carried both risk alleles exhibited a risk ratio that differed significantly from 1 (risk ratio = 16.2, P = 0.008, 95% CI = 2.1-128.3). After controlling for these genotypes, female genderwas also significantly associated with increased risk of developing AD (risk ratio = 5.1, P = 0.02, 95% CI =1.2-21.1). Neither age at recruitment noryears of education made significant contributions to the model.

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Documento generato il 26/01/20 alle ore 22:08:07