BACKGROUND: Numerous studies have tested for associations between common variants of the angiotensin-converting enzyme gene (ACE) and late-onset Alzheimer disease (AD), but results have been inconclusive. METHODS: Relevant studies were systematically identified, and data were abstracted according to predefined criteria. RESULTS: The odds ratio (OR) for AD in individuals with the I allele of the ACE D/I polymorphism compared with those with the DD genotype was 1.27 (95% CI, 1.10 to 1.47; p < 0.001). Heterogeneity between studies was significant (p < 0.001) but not in strata defined by race and age (p > or = 0.10). The risk of AD associated with the I allele appeared to be higher among Asians (OR 2.44; 95% CI, 1.68 to 3.53) when compared with the risk among Caucasians (OR 1.18; 95% CI, 1.02 to 1.37) (p for comparison < 0.001), and in younger cases (mean age 65 to 74 years) (OR 1.54; 95% CI, 1.23 to 1.93) when compared with the risk in older cases (OR 1.13; 95% CI, 0.95 to 1.35) (p for comparison = 0.03). CONCLUSIONS: The I allele of the ACE D/I polymorphism is associated with an increased risk of late-onset AD. Further study of the pathogenetic characteristics of this allele and independent confirmation of the association in larger studies are warranted.
BACKGROUND: Numerous studies have tested for associations between common variants of the angiotensin-converting enzyme gene (ACE) and late-onset Alzheimer disease (AD), but results have been inconclusive. METHODS: Relevant studies were systematically identified, and data were abstracted according to predefined criteria. RESULTS: The odds ratio (OR) for AD in individuals with the I allele of the ACE D/I polymorphism compared with those with the DD genotype was 1.27 (95% CI, 1.10 to 1.47; p < 0.001). Heterogeneity between studies was significant (p < 0.001) but not in strata defined by race and age (p > or = 0.10). The risk of AD associated with the I allele appeared to be higher among Asians (OR 2.44; 95% CI, 1.68 to 3.53) when compared with the risk among Caucasians (OR 1.18; 95% CI, 1.02 to 1.37) (p for comparison < 0.001), and in younger cases (mean age 65 to 74 years) (OR 1.54; 95% CI, 1.23 to 1.93) when compared with the risk in older cases (OR 1.13; 95% CI, 0.95 to 1.35) (p for comparison = 0.03). CONCLUSIONS: The I allele of the ACE D/I polymorphism is associated with an increased risk of late-onset AD. Further study of the pathogenetic characteristics of this allele and independent confirmation of the association in larger studies are warranted.
Authors: Paul A Insel; Stuart Kornfeld; Philip W Majerus; Andrew R Marks; Paul A Marks; Arnold S Relman; Bruce F Scharschmidt; Thomas P Stossel; Ajit P Varki; Stephen J Weiss; Jean D Wilson Journal: J Clin Invest Date: 2004-10 Impact factor: 14.808
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