Angiotensin converting enzyme deletion allele in different kinds of dementia disorders

doi:10.1016/S0304-3940(99)00329-8

Neuroscience Letters

Volume 267, Issue 2, 28 May 1999, Pages 97-100

https://doi.org/10.1016/S0304-3940(99)00329-8 Get rights and content

Abstract

In order to verify the association of Angiotensin converting enzyme (ACE) gene with different kinds of dementia, as well as its association with APO-E (genotype), we performed ACE genotyping in subjects with late-onset probable Alzheimer's disease (LOAD, n=64), early-onset probable Alzheimer's disease (EOAD, n=32), possible Alzheimer's disease (pAD, n=44), vascular dementia (VD, n=12), age-associated memory impairment (AAMI, n=15) and 40 healthy age-matched controls, who were previously characterized for APO-E. After the principal component analysis ACE D and Apo-Eϵ₄ alleles disclosed the highest prevalence in the cognitively impaired groups of subjects, Apo-Eϵ₄ being more specific for LOAD and pAD. ACE D allele seems to be an unspecific susceptibility factor for mental decline.

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Acknowledgements

The authors are grateful to Professors Arnaldo Fravolini, Carlo Riccardi and Violetta Cecchetti for their support.

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Association between apolipoprotein E gene polymorphism and the risk of vascular dementia: A meta-analysis
2012, Neuroscience Letters
Citation Excerpt :
Three studies came from the same institution and involved the same population, so only the newest data was included in the analysis [30–32]. Thus, 29 studies were included in the final meta-analysis [2–6,9–19,22,24,25,27–29,32,34,36,38–41], which contained 1763 VaD cases and 4534 controls. The countries of these studies included Italy, Finland, Hungary, France, Spain, China, Japan, Korea, and India.
It remains controversial regarding the association between Apolipoprotein E (ApoE) gene polymorphism and the risk of vascular dementia (VaD). The present meta-analysis was performed to derive a more precise estimation of the relationship. The meta-analysis was performed by searching PubMed, Embase and Web of Science databases. A total of 29 studies included 1763 VaD cases and 4534 controls were identified. The results showed evidence for significant association between ApoE ɛ4 mutation and VaD risk (for ɛ3/ɛ4 vs. ɛ3/ɛ3: OR = 1.65, 95% CI = 1.40–1.94, p-value < 0.00001; for ɛ4/ɛ4 vs. ɛ3/ɛ3: OR = 3.17, 95% CI = 2.09–4.80, p-value < 0.00001; for ɛ4 allele vs. ɛ3 allele: OR = 1.72, 95% CI = 1.40–2.12, p-value < 0.00001). The similar results were obtained in the subgroup analysis based on ethnicity. In summary, the present meta-analysis suggests an association between ApoE ɛ4 mutation and increased risk of VaD. However, due to the small sample size in most of the included studies and the selection bias existed in some studies, the results should be interpreted with caution.
Epidemiology of non-AD dementias
2004, Clinical Neuroscience Research
Dementia is a common neurodegenerative disorder that affects about 10% of the population over 65 years of age. A distinction can be made between primary degenerative dementias and dementia secondary to other diseases. This review focuses on the primary non-Alzheimer's disease (AD) dementias: vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). VaD is after AD most frequent subtype of dementia with a prevalence of about 1%, ranging from 0 to 10% mainly depending on the age group investigated and the criteria used. Its incidence rate is between 1.5 and 4.1 per 1000 person-years, with no clear difference between men and women and with possibly a higher incidence in East Asia compared to Canada and Europe. Most of the VaD cases are sporadic although there are some rare familial forms of VaD as cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy and familial cerebral amyloid angiopathy. Important risk factors for sporadic VaD are cerebrovascular pathology (brain infarction, white matter lesions and brain atrophy), midlife hypertension, and diabetes leading to increasing risk ratios. A protective effect is often found for education and moderate use of alcohol. The association between VaD and amyloid β, cholesterol, and statin use remains unclear yet. DLB and FTD are less frequent forms of dementia with prevalence rates of, respectively, 0.1–0.6 and 0.002–0.015%. FTD affects people in their middle age, accounting for up to 10–20% of the presenile dementia cases. About 14% of the FTD cases are caused by an autosomal dominant tau-mutation. However, since the prevalence of sporadic FTD is relatively low, population-based epidemiological studies are hard to perform and no non-genetic risk factors are known yet. DLB is a relative common form of dementia in old age accounting for 15–20% of cases in hospital autopsy case-series. The only known possible risk factor for DLB is the presence of an apolipoprotein E ε4 allele.
Angiotensin-converting enzyme and alpha-2-macroglobulin gene polymorphisms are not associated with Alzheimer's disease in Colombian patients
2004, Journal of the Neurological Sciences
Polymorphisms in alpha-2-macroglobulin (A2M) and angiotensin-converting enzyme (ACE) genes have been considered as risk factors for Alzheimer's disease (AD) independently of the risk conferred by the apolipoprotein E ε4 allele (APOEε4) in diverse populations. In the present study, we have analysed the distribution of genotypes and alleles of the insertion/deletion (I/D) polymorphisms of ACE and A2M in 83 AD patients and 69 normal controls in Colombia. Our results showed that there is no association between the I/D polymorphisms of ACE and A2M with AD (P=0.788 and P=0.538, respectively). Using logistic regression and multiple correlation analysis (MCA), we confirmed that the main risk factor associated and consistently grouped with AD patients in this population is APOEε4, but this association was not observed with alleles and genotypes of ACE and A2M.
A polymorphism in the angiotensin 1-converting enzyme gene is associated with damage to cerebral cortical white matter in Alzheimer's disease
2004, Neuroscience Letters
The impact of the insertion (I)/deletion (D) (I/D) polymorphism in the angiotensin 1-converting enzyme (ACE) gene on the extent of white matter myelin loss (ML) was investigated in four regions of the cerebral cortex in an autopsy-confirmed series of 93 patients with Alzheimer's disease (AD). The possible influence of APO E ε4 allele acting in concert with ACE D allele was assessed. The extent of ML did not differ between D/D, I/D and I/I genotype groups when data from all four brain regions were combined. However, separate analysis showed that the frontal and temporal cortex tended to be affected more severely by ML in patients with D/D genotype compared to those with I/D and I/I genotypes. Stratification according to APO E ε4 allele revealed a greater overall ML in patients bearing at least one copy of ACE D allele and one APO E ε4 allele, especially in individuals homozygous for both. The APO E ε4 allele may therefore act synergistically in patients with AD (and other subjects) bearing ACE D/D genotype to increase the risk of ML, perhaps through transient ischaemic episodes consequent upon poor cardiac output associated with coronary atherosclerosis in patients with the APO E ε4 allele.
Apolipoprotein E, angiotensin-converting enzyme and α-1-antichymotrypsin genotypes are not associated with post-stroke dementia
2003, Journal of the Neurological Sciences
There is evidence that indicates the involvement of environmental and genetic factors in the pathogenesis of post-stroke dementia (PSD). In the present work, we examined different polygenic influences on the risk of PSD in a series of stroke patients. We studied 150 consecutive patients evaluated 3 months after suffering acute strokes. All patients were evaluated with a prospective standard protocol and genotyped for vascular disease-associated polymorphisms in the genes coding for apolipoprotein E (including apoE coding and apoE promoter polymorphisms), angiotensin-converting enzyme (ACE) and α-1-antichymotrypsin (ACT). Thirty-two cases (21.3%) resulted in dementia 3 months after the stroke. In patients with PSD, the frequency of apoE ε4 (0.08), ACE-D (0.64), ACT-A (0.62) alleles and apoE gene promoter polymorphisms (−491/A, 0.88; −427/C, 0.02) was similar to that of patients without PSD (apoE ε4: 0.10, p=0.79; ACE-D: 0.56, p=0.36; ACT-A: 0.51, p=0.21; −491/A: 0.86, p=1.00; −427/C: 0.08, p=0.29). Our data indicate that PSD is not associated with the genetic risk factors of vascular dementia (VD) that were studied, and that additional factors may contribute to the pathogenesis of PSD.
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2021, PLoS ONE

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Angiotensin converting enzyme deletion allele in different kinds of dementia disorders

Abstract

Section snippets

Acknowledgements

Eur. J. Pharmacol.

Lancet

J. Psychiatr. Res.

Neurosci. Lett.

The deletion allele of the angiotensin I converting enzyme gene as a genetic susceptibility factor for cognitive impairment

Neurosci. Lett.

Angiotensin converting enzyme gene deletion allele is independently and strongly associated with coronary atherosclerosis and myocardial infarction

Br. Heart J.

La chimica e l'Industria

Angiotensin converting enzyme I/D polymorphism and arterial wall thickness in a general population. The Vobarno Study

Circulation