Meta-Analysis of the Association of the Cathepsin D Ala224Val Gene Polymorphism with the Risk of Alzheimer’s Disease: A HuGE Gene-Disease Association Review

• Published in: American journal of epidemiology Vol. 159; no. 6; pp. 527 - 536
• Main Authors: Ntais, Christos, Polycarpou, Anastasia, Ioannidis, John P. A.
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 15.03.2004; Oxford Publishing Limited (England)
• Subjects: Alzheimer disease; Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Alzheimer's disease; Analysis. Health state; Apolipoproteins E - genetics; Biological and medical sciences; cathepsin D; Cathepsin D - genetics; confidence interval; CTSD; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Epidemiology; Gene expression; General aspects; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; genetics; Genotype & phenotype; Health risk assessment; Heterogeneity; Humans; Medical sciences; meta-analysis; Neurology; odds ratio; polymorphism (genetics); Polymorphism, Genetic - genetics; Public health. Hygiene; Public health. Hygiene-occupational medicine; Risk; Risk factors; Alzheimer disease; Risk; Review; Epidemiology; Metaanalysis; Association; Gene; Genetics; Aspartic endopeptidases; Degenerative disease; Cathepsin D; polymorphism (genetics); CTSD; Public health; Human; Nervous system diseases; Enzyme; meta-analysis; Cerebral disorder; Peptidases; Central nervous system disease; Risk factor; Hydrolases; Bibliographic review; Polymorphism
• ISSN: 0002-9262; 1476-6256; 0002-9262
• DOI: 10.1093/aje/kwh069

A C-to-T polymorphism in exon 2 of the cathepsin D gene encoding cathepsin D (CTSD) has been implicated as a risk factor for Alzheimer’s disease. The authors performed a meta-analysis of 14 studies (16 comparisons) with CTSD genotyping (3,174 Alzheimer’s disease cases and 3,298 controls). Overall, the random effects odds ratio for the T versus the C allele was 1.17 (95% confidence interval (CI): 0.95, 1.44), with some between-study heterogeneity (p < 0.01). There was significant between-study heterogeneity but no evidence of a significant association when the first hypothesis-generating study was excluded from the calculations (odds ratio (OR) = 1.11, 95% CI: 0.91, 1.35; p = 0.29). The summary odds ratio for T carriers versus T noncarriers was similar in subjects carrying or not carrying an apolipoprotein E ε4 allele (APOE*4). The increased susceptibility to Alzheimer’s disease conferred by APOE*4 carriage tended to be more prominent in the presence of the T allele (random effects OR = 6.07, 95% CI: 4.19, 8.79, and OR = 4.09, 95% CI: 3.15, 5.31, in T carriers and noncarriers, respectively). The meta-analysis shows that the CTSD polymorphism is not a major risk factor for Alzheimer’s disease, although a small effect or an enhancement of the APOE*4 effect cannot be excluded.