Association of Polymorphisms in the Angiotensin-Converting Enzyme Gene with Alzheimer Disease in an Israeli Arab Community
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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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ACE and ADAM10 were previously reported as Alzheimer's disease candidate genes but were not replicated in some subsequent studies.
“ACE and ADAM10 were previously reported as Alzheimer’s disease candidate genes18–22 but were not replicated in some subsequent studies23–25.”
From Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing (2019) · cites this paper as [21]
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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
- bronze
- doi.org
- Licence
- 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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