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. 2006 May;78(5):871-877.
doi: 10.1086/503687. Epub 2006 Mar 16.

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

Yan Meng  1 , Clinton T Baldwin  2 , Abdalla Bowirrat  1 , Kristin Waraska  2 , Rivka Inzelberg  3 , Robert P Friedland  4 , Lindsay A Farrer  5
Affiliations

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

Yan Meng et al. Am J Hum Genet. 2006 May.

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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Figures

Figure 1
Figure 1
LD block structure in the DCP1 region. The upper triangle shows LD calculated using the r2 measure, and the lower triangle shows LD calculated using the D′ measure.
Figure 2
Figure 2
Proposed mechanisms for influence of ACE on development of AD via a pathway leading to increased production of the toxic form of Aβ (Aβ42) or through the action of vascular risk factors (see text for details).
See this image and copyright information in PMC

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References

Web Resources

    1. Daniel J. Schaid's Web site, http://mayoresearch.mayo.edu/mayo/research/biostat/schaid.cfm (for Haplo.stats v1.1.1)
    1. dbSNP, http://www.ncbi.nlm.nih.gov/projects/SNP/ (primary source for SNP information)
    1. International HapMap Project, http://www.hapmap.org/
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for AD, APOE, and ACE)
    1. RESCUE-ESE Web Server, http://genes.mit.edu/burgelab/rescue-ese/

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