TY - JOUR
T1 - Association of polymorphisms in the angiotensin-converting enzyme gene with Alzheimer disease in an Israeli Arab community
AU - Meng, Yan
AU - Baldwin, Clinton T.
AU - Bowirrat, Abdalla
AU - Waraska, Kristin
AU - Inzelberg, Rivka
AU - Friedland, Robert P.
AU - Farrer, Lindsay A.
N1 - Funding Information:
This work was supported by grants from Fonds de la Recherche en Santé, the National Institutes of Health (U01-AG17173, R01-AG09029, and P30-AG13846), the Institute for the Study of Aging, the GOJO Corp (Akron, OH), the Fullerton Family Charitable Trust, the Nickman family, and the Florence and Joseph Mandel Research Fund.
PY - 2006/5
Y1 - 2006/5
N2 - 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 × 0-7). 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 × 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.
AB - 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 × 0-7). 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 × 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.
UR - http://www.scopus.com/inward/record.url?scp=33646048350&partnerID=8YFLogxK
U2 - 10.1086/503687
DO - 10.1086/503687
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C2 - 16642441
AN - SCOPUS:33646048350
SN - 0002-9297
VL - 78
SP - 871
EP - 877
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 5
ER -