Journal Article

Large Meta-Analysis Establishes the <i>ACE</i> Insertion-Deletion Polymorphism as a Marker of Alzheimer's Disease

Donald J. Lehmann, Mario Cortina-Borja, Donald R. Warden, A. David Smith, Kristel Sleegers, Jonathan A. Prince, Cornelia M. van Duijn and Patrick G. Kehoe

in American Journal of Epidemiology

Published on behalf of Johns Hopkins Bloomberg School of Public Health

Volume 162, issue 4, pages 305-317
Published in print August 2005 | ISSN: 0002-9262
Published online August 2005 | e-ISSN: 1476-6256 | DOI: http://dx.doi.org/10.1093/aje/kwi202
Large Meta-Analysis Establishes the ACE Insertion-Deletion Polymorphism as a Marker of Alzheimer's Disease

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Apolipoprotein E ε4 (APOE*4) is the only fully established susceptibility allele for Alzheimer's disease. One of the most studied candidates is the insertion (I)/deletion (D) polymorphism (indel) of the gene for angiotensin I-converting enzyme (ACE). This study aimed to clarify its association with Alzheimer's disease. The meta-analysis included 39 samples, comprising 6,037 cases of Alzheimer's disease and 12,099 controls, using mainly primary data. Potential interactions with gender, age, ethnic group, and carrier status of the apolipoprotein E ε4 allele were all examined. D homozygotes were at reduced risk of Alzheimer's disease (odds ratio = 0.81, 95% confidence interval: 0.72, 0.90; corrected p = 0.0004); I homozygotes showed no association with Alzheimer's disease, while heterozygotes were at increased risk. Although there were clear differences among the three ethnic groups examined (North Europeans, South Caucasians, and East Asians), in all groups D homozygotes were at reduced risk. These results confirm the association of the angiotensin I-converting enzyme indel with Alzheimer's disease across diverse populations, although this is probably due to linkage disequilibrium with the true risk factor. Further, in North Europeans, both association and Hardy-Weinberg analysis suggested partial heterosis, that is, an increased risk for heterozygotes, due to a hidden interaction with another, as yet unknown, risk factor. This interaction warrants further investigation.

Keywords: Alzheimer disease; heterogeneity; meta-analysis; ACE, angiotensin I-converting enzyme (protein); ACE, angiotensin I-converting enzyme (gene); APOE*4, apolipoprotein E ε4 (allele)

Journal Article.  7061 words.  Illustrated.

Subjects: Public Health and Epidemiology

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