title: Association of polymorphisms in the Angiotensin-converting enzyme gene with Alzheimer disease in an Israeli Arab community.
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.
authors.affiliation: Department of Medicine (Genetics Program), Boston University School of Medicine, Boston.
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Center for Human Genetics, Boston University School of Medicine, Boston.
authors.forename: Clinton T
authors.initials: CT
authors.lastname: Baldwin
authors.affiliation: Department of Medicine (Genetics Program), Boston University School of Medicine, Boston.
authors.forename: Abdalla
authors.initials: A
authors.lastname: Bowirrat
authors.affiliation: Center for Human Genetics, Boston University School of Medicine, Boston.
authors.forename: Kristin
authors.initials: K
authors.lastname: Waraska
authors.affiliation: Department of Neurology, Hillel Yaffe Medical Center, Hadera and Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Rivka
authors.initials: R
authors.lastname: Inzelberg
authors.affiliation: Department of Neurology, Case Western Reserve University, Cleveland.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Friedland
authors.affiliation: 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: farrer@bu.edu.
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Farrer
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics*; D018912:Arabs / Q000235:genetics; D016022:Case-Control Studies; D004251:DNA Transposable Elements; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007557:Israel / Q000208:ethnology; D008875:Middle Aged; D008957:Models, Genetic; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion
chemical_list: D004251:DNA Transposable Elements; D007703:Peptidyl-Dipeptidase A