Cited by 72Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchGenetic Associations and Epidemiology

Association of Polymorphisms in the Angiotensin-Converting Enzyme Gene with Alzheimer Disease in an Israeli Arab Community

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Meng, Yan, Baldwin, Clinton T., Bowirrat, Abdalla, Waraska, Kristin, Inzelberg, Rivka, Friedland, Robert P., Farrer, Lindsay A.·2006·The American Journal of Human Genetics

Abstract

Several lines of evidence support for a role of angiotensin converting enzyme (ACE) in Alzheimer disease (AD). Most genetic studies have focused on an Alu insertion/deletion (I/D) polymorphism in the ACE gene (DCP1) and have yielded conflicting results. We evaluated the association between 15 single-nucleotide polymorphisms (SNPs) in DCP1, including the I/D variant, and AD in a sample of 92 patients with AD and 166 nondemented controls from an inbred Israeli Arab community. Although there was no evidence for association between AD and I/D, we observed significant association with SNPs rs4343 (P = .00001) and rs4351 (P = .01). Haplotype analysis revealed remarkably significant evidence of association with the SNP combination rs4343 and rs4351 (global P = 7.5 x 10(-7)). Individuals possessing the haplotype "GA" (frequency 0.21 in cases and 0.01 in controls) derived from these SNPs had a 45-fold increased risk of developing AD (95% CI 6.0-343.2) compared with those possessing any of the other three haplotypes. Longer range haplotypes including I/D were even more significant (lowest global P = 1.1 x 10(-12)), but the only consistently associated alleles were in rs4343 and rs4351. These results suggest that a variant in close proximity to rs4343 and rs4351 modulates susceptibility to AD in this community.

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Crossref · 10.1086/503687

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Authors
Meng, Y., Baldwin, C. T., Bowirrat, A., Waraska, K., Inzelberg, R., Friedland, R. P., & Farrer, L. A.
Affiliations
  • Boston University (US)
  • Technion – Israel Institute of Technology (IL)
  • Case Western Reserve University (US)
Corresponding author
Farrer, Lindsay A.
Venue
The American Journal of Human Genetics
Publisher
Elsevier BV
Published
2006-05
Volume
78
Issue
5
Pages
871-877
ISSN
0002-9297 (ISSN-L)
OpenAlex
W1978231609
Cited by
72
References
43
Citations by year
2026: 1 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 4 · 2019: 5 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 3 · 2014: 5 · 2013: 3 · 2012: 6
FWCI
4.78
Type
journal article
Language
en
Open access
Locations
  • The American Journal of Human Genetics (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (U01AG017173, P30AG013846, R01AG009029)
Topics
  • Health Sciences › Medicine › Physiology › 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 gene, single nucleotide polymorphisms, insertion/deletion polymorphism, haplotype association, genetic susceptibility, inbred populations
MeSH terms
Aged, Alzheimer Disease, DNA Transposable Elements, Gene Frequency, Haplotypes, Humans, Israel, Peptidyl-Dipeptidase A, Middle Aged, Models, Genetic, Polymorphism, Genetic, Genetic Variation, Case-Control Studies, Sequence Deletion, Arabs, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide

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