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PMID: 16642441 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Association of polymorphisms in the Angiotensin-converting enzyme gene with Alzheimer disease in an Israeli Arab community.

American journal of human genetics ·Vol. 78 ·No. 5 ·2006-05-00 ·Pages 871-877

Meng Y, Baldwin CT, Bowirrat A, Waraska K, Inzelberg R, Friedland RP, Farrer LA

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.

MeSH Terms
Aged Alzheimer Disease/ethnology,genetics Arabs/genetics Case-Control Studies DNA Transposable Elements Gene Frequency Genetic Predisposition to Disease Genetic Variation Haplotypes Humans Israel/ethnology Middle Aged Models, Genetic Peptidyl-Dipeptidase A/genetics Polymorphism, Genetic Polymorphism, Single Nucleotide Sequence Deletion
Chemicals
DNA Transposable Elements Peptidyl-Dipeptidase A
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Meng Yan
Department of Medicine (Genetics Program), Boston University School of Medicine, Boston.
Baldwin Clinton T
Center for Human Genetics, Boston University School of Medicine, Boston.
Bowirrat Abdalla
Department of Medicine (Genetics Program), Boston University School of Medicine, Boston.
Waraska Kristin
Center for Human Genetics, Boston University School of Medicine, Boston.
Inzelberg Rivka
Department of Neurology, Hillel Yaffe Medical Center, Hadera and Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Friedland Robert P
Department of Neurology, Case Western Reserve University, Cleveland.
Farrer Lindsay A
Department of Medicine (Genetics Program), Boston University School of Medicine, Boston; Department of Neurology, Boston University School of Medicine, Boston; Department of Genetics & Genomics, Boston University School of Medicine, Boston; Departments of Biostatistics and Epidemiology, Boston University School of Public Health, Boston. Electronic address: [email protected].
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
DOI
10.1086/503687
Email
[email protected]
Published
2006-05-00
Epub
2006-00-16
Pages
871-877
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1474030
Subset
IM
Grants
NIA NIH HHS · R01-AG09029 · United States
NIA NIH HHS · R01 AG009029 · United States
NIA NIH HHS · U01-AG17173 · United States
NIA NIH HHS · P30 AG013846 · United States
NIA NIH HHS · U01 AG017173 · United States
NIA NIH HHS · P30-AG13846 · United States
External Links
PubMed source DOI: 10.1086/503687 PMC Full Text View journal details
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