Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Is Not a Major Determining Factor in the Development of Sporadic Alzheimer Disease: Evidence from an Updated Meta-Analysis
Open accessAbstract
Angiotensin-converting enzyme gene (ACE) insertion/deletion (I/D) polymorphism have long been linked to sporadic Alzheimer disease (SAD), but the established data remained controversial. To clarify this inconsistency, a comprehensive meta-analysis was conducted. Through searching of Pubmed, Embase, Alzgene, China National Knowledge Infrastructure (CNKI) and manually searching relevant references, 53 independent studies from 48 articles were included, involving a total of 8153 cases and 14932 controls. The strength of association was assessed by using odds ratios (ORs) with 95% confidence intervals (CIs). Further stratified analyses and heterogeneity analyses were tested, as was publication bias. Overall, significant associations were revealed between I/D polymorphism and SAD risk using allelic comparison (OR = 1.09, 95%CI = 1.01-1.17, p = 0.030), homozygote comparison (OR = 1.17, 95%CI = 1.01-1.34, p = 0.030) and the dominant model (OR = 1.16, 95%CI = 1.04-1.29, p = 0.008), but they were not sufficiently robust to withstand the false-positive report probability (FPRP) analyses. Otherwise, in subgroup analyses restricted to the high quality studies, the large sample size studies and studies with population-based controls, no significant association was observed in any genetic models. In summary, the current meta-analysis suggested that the ACE I/D polymorphism is unlikely to be a major determining factor in the development of SAD.
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ACE and ADAM10 were previously reported as Alzheimer's disease candidate genes but were not replicated in some subsequent studies.
“ACE and ADAM10 were previously reported as Alzheimer’s disease candidate genes18–22 but were not replicated in some subsequent studies23–25.”
From Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing (2019) · cites this paper as [23]
These studies yielded inconsistent results, and our work reports a clear genome-wide association in NHW at the ACE locus.
“However, these studies yielded inconsistent results23, and our work reports a clear genome-wide association in NHW at this locus.”
From Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing (2019) · cites this paper as [23]
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Alzheimer Disease Genetics Consortium (ADGC), Kunkle, B. W., The European Alzheimer’s Disease Initiative (EADI), Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), Genetic and Environmental Risk in AD/Defining Genetic, P. A. E. R. F. A. D. C. (., Grenier-Boley, B., Sims, R., Bis, J. C., Damotte, V., Naj, A. C., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0358-2 · Cited by 2,946 · see citing works
- Authors
- Wang, X.-B., Cui, N.-H., Yang, J., Qiu, X.-P., Gao, J.-J., Yang, N., & Zheng, F.
- Affiliations
- Zhengzhou Children's Hospital (CN)
- Zhongnan Hospital of Wuhan University (CN)
- Corresponding author
- Zheng, Fang
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-10-31
- Volume
- 9
- Issue
- 10
- Pages
- e111406
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4216072
- OpenAlex
- W1976446430
- Cited by
- 15
- References
- 89
- Citations by year
- 2023: 1 · 2021: 1 · 2020: 1 · 2019: 5 · 2018: 2 · 2017: 4 · 2015: 1
- FWCI
- 0.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Key Research and Development Program of China (2012CB720600)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- angiotensin-converting enzyme, ACE I/D polymorphism, sporadic Alzheimer's disease, genetic susceptibility, disease risk, false-positive report probability, genetic association
- MeSH terms
- Alleles, Alzheimer Disease, Humans, Peptidyl-Dipeptidase A, Probability, Risk Factors, Odds Ratio, Case-Control Studies, Publication Bias, Sample Size, Genetic Heterogeneity, Genetic Predisposition to Disease, INDEL Mutation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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