Large meta-analysis establishes the ACE insertion-deletion polymorphism as a marker of Alzheimer's disease

The Oxford Project to Investigate Memory and Ageing (OPTIMA), Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
American Journal of Epidemiology (Impact Factor: 4.98). 09/2005; 162(4):305-17. DOI: 10.1093/aje/kwi202
Source: PubMed

ABSTRACT Apolipoprotein E ε4 (APOE*4) is the only fully established susceptibility allele for Alzheimer's disease. One of the most studied candidates is the insertion
(I)/deletion (D) polymorphism (indel) of the gene for angiotensin I-converting enzyme (ACE). This study aimed to clarify its association with Alzheimer's disease. The meta-analysis included 39 samples, comprising
6,037 cases of Alzheimer's disease and 12,099 controls, using mainly primary data. Potential interactions with gender, age,
ethnic group, and carrier status of the apolipoprotein E ε4 allele were all examined. D homozygotes were at reduced risk of Alzheimer's disease (odds ratio = 0.81, 95% confidence interval: 0.72, 0.90; corrected
p = 0.0004); I homozygotes showed no association with Alzheimer's disease, while heterozygotes were at increased risk. Although there were
clear differences among the three ethnic groups examined (North Europeans, South Caucasians, and East Asians), in all groups
D homozygotes were at reduced risk. These results confirm the association of the angiotensin I-converting enzyme indel with
Alzheimer's disease across diverse populations, although this is probably due to linkage disequilibrium with the true risk
factor. Further, in North Europeans, both association and Hardy-Weinberg analysis suggested partial heterosis, that is, an
increased risk for heterozygotes, due to a hidden interaction with another, as yet unknown, risk factor. This interaction
warrants further investigation.

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    ABSTRACT: Introduction Alzheimer’s disease (AD) is a progressive, neurodegenerative disease. Many studies proposed an association of the insertion (I)/deletion (D) polymorphism (indel) in intron 16 of the gene for angiotensin I-converting enzyme (ACE) on chromosome 17q23 with Alzheimer’s disease. ACE indel and related haplotypes associated with AD risk have reduced plasma ACE whereas protective genotypes have elevated ACE. Object To investigate whether there is a correlation between polymorphisms of the ACE I/D locus gene and AD in Egyptian patients and to determine whether there is a difference in ACE activity in the plasma of clinically diagnosed AD patients. Methods Subjects of this study are 84 dementia patients diagnosed as having Alzheimer’s disease, 45 males and 39 females aged 65 ± 7 years from the Geriatric Department at Ain-Shams University Hospitals and 86 individuals as non dementia controls, 44 males and 42 females aged 63 ± 6 years. All subjects were genotyped for the common insertion/deletion polymorphisms for ACE gene locus, and ACE plasma activity assay was measured for AD patients. Results There was statistically significant difference in the frequency of the ACE insertion/deletion alleles between the cases and controls where the I allele distribution in AD cases and controls was 74% vs. 15%, and the I/I genotype frequency was 60% vs. 5%, respectively. They both reached a statistical significance range (I allele frequency: OR = 3.714, 95% CI 1.311–10.523, p < 0.01; I/I genotype frequency: OR = 3.18 95% CI 2.33–4.33, p < 0.01). But no significant difference in ACE plasma level was found between different genotypes in our AD patients. Conclusions Our present study supports the hypothesis of implication (I allele) of ACE gene polymorphism in the development of AD. On the other hand, we did not find significant difference in plasma ACE activities when compared with different studied genotypes.
    Egyptian Journal of Medical Human Genetics 06/2014; 15(4). DOI:10.1016/j.ejmhg.2014.06.001
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    ABSTRACT: Alzheimer's disease (AD) is a prevalent disorder and the most common cause of dementia in elderly populations. Genetic and environmental factors together play a role in developing late onset Alzheimer's disease (LOAD). According to the recent published papers, ACE is one of the candidate susceptibility genes for LOAD. In this study, allele and genotype frequencies for rs4291 and rs1799752 polymorphisms of ACE gene, for 100 Iranian patients, affected with AD and 100 healthy controls were compared using Chi-square test. No statistically significant differences were found in genotype and allele frequencies of rs4291 and rs1799752 polymorphisms between our LOAD patients and controls. The pair-wise haplotype analysis of rs4291 -240 A/T and rs1799752 Alu I/D polymorphisms were also performed, but no significant associations were identified.
    AFRICAN JOURNAL OF BIOTECHNOLOGY 04/2012; 11(22-11):5982-5987. · 0.57 Impact Factor
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    Topics in the Prevention, Treatment and Complications of Type 2 Diabetes, 11/2011; , ISBN: 978-953-307-590-7