Cited by 199Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchGenetic Associations and Epidemiology

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

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Lehmann, Donald J., Cortina-Borja, Mario, Warden, Donald R., Smith, A. David, Sleegers, Kristel, Prince, Jonathan A., van Duijn, Cornelia M., Kehoe, Patrick G.·2005·American Journal of Epidemiology

DOI 10.1093/aje/kwi202

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Abstract

Apolipoprotein E epsilon4 (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 epsilon4 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.

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Authors: Lehmann, D. J., Cortina-Borja, M., Warden, D. R., Smith, A. D., Sleegers, K., Prince, J. A., van Duijn, C. M., & Kehoe, P. G.
Affiliations: University of Oxford (GB)
Corresponding author: Lehmann, Donald J.
ORCID: Smith, A. David
Sleegers, Kristel
Kehoe, Patrick G.
Venue: American Journal of Epidemiology
Publisher: Oxford University Press (OUP)
Published: 2005-08-15
Volume: 162
Issue: 4
Pages: 305-317
ISSN: 0002-9262 (ISSN-L)
1476-6256
DOI: 10.1093/aje/kwi202
OpenAlex: W2044936845
Cited by: 199
References: 79
Citations by year: 2026: 3 · 2025: 1 · 2024: 6 · 2023: 8 · 2022: 3 · 2021: 9 · 2020: 6 · 2019: 9 · 2018: 8 · 2017: 9 · 2016: 5 · 2015: 7 · 2014: 15 · 2013: 9 · 2012: 9
FWCI: 2.16
Type: journal article
Language: en
Open access: green
hdl.handle.net
Licence: other-oa
Locations: American Journal of Epidemiology (publishedVersion)
PubMed (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
Bristol Research (University of Bristol) (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
UCL Discovery (University College London) (submittedVersion)
Funders: Bristol-Myers Squibb
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords: Alzheimer's disease, angiotensin-converting enzyme, ACE I/D polymorphism, APOE ε4, genetic susceptibility, genetic association, linkage disequilibrium, heterosis, ethnic differences, Hardy-Weinberg equilibrium, risk factors
MeSH terms: Aged, Alzheimer Disease, Apolipoproteins E, Ethnicity, Female, Humans, Hybrid Vigor, Peptidyl-Dipeptidase A, Male, Middle Aged, Polymorphism, Genetic, Confidence Intervals, Apolipoprotein E4

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

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