Pharmacogenetics of Angiotensin-Converting Enzyme Inhibitors in Patients with Alzheimer's Disease Dementia

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dc.citation.issue4
dc.citation.volume15
dc.contributor.authorde Oliveira, Fabricio Ferreira [UNIFESP]
dc.contributor.authorChen, Elizabeth Suchi [UNIFESP]
dc.contributor.authorSmith, Marilia Cardoso [UNIFESP]
dc.contributor.authorFerreira Bertolucci, Paulo Henrique [UNIFESP]
dc.coverageSharjah
dc.date.accessioned2020-07-02T18:52:03Z
dc.date.available2020-07-02T18:52:03Z
dc.date.issued2018
dc.description.abstractBackground: While the angiotensin-converting enzyme degrades amyloid-beta, angiotensin-converting enzyme inhibitors (ACEis) may slow cognitive decline by way of cholinergic effects, by increasing brain substance P and boosting the activity of neprilysin, and by modulating glucose homeostasis and augmenting the secretion of adipokines to enhance insulin sensitivity in patients with Alzheimer's disease dementia (AD). We aimed to investigate whether ACE gene polymorphisms rs1800764 and rs4291 are associated with cognitive and functional change in patients with AD, while also taking APOE haplotypes and anti-hypertensive treatment with ACEis into account for stratification. Methods: Consecutive late-onset AD patients were screened with cognitive tests, while their caregivers were queried for functional and caregiver burden scores. Prospective pharmacogenetic correlations were estimated for one year, considering APOE and ACE genotypes and haplotypes, and treatment with ACEis. Results: For 193 patients, minor allele frequencies were 0.497 for rs1800764 - C (44.6% heterozygotes) and 0.345 for rs4291 - T (38.9% heterozygotes), both in Hardy-Weinberg equilibrium. Almost 94% of all patients used cholinesterase inhibitors, while 155 (80.3%) had arterial hypertension, and 124 used ACEis. No functional impacts were found regarding any genotypes or pharmacological treatment. Either for carriers of ACE haplotypes that included rs1800764 - T and rs4291 - A, or for APOE4- carriers of rs1800764 - T or rs4291 - T, ACEis slowed cognitive decline independently of blood pressure variations. APOE4+ carriers were not responsive to treatment with ACEis. Conclusion: ACEis may slow cognitive decline for patients with AD, more remarkably for APOE4- carriers of specific ACE genotypes.en
dc.description.affiliationFed Univ Sao Paulo UNIFESP, Escola Paulista Med, Dept Neurol & Neurosurg, Sao Paulo, SP, Brazil
dc.description.affiliationFed Univ Sao Paulo UNIFESP, Escola Paulista Med, Dept Morphol & Genet, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespFed Univ Sao Paulo UNIFESP, Escola Paulista Med, Dept Neurol & Neurosurg, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespFed Univ Sao Paulo UNIFESP, Escola Paulista Med, Dept Morphol & Genet, Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipCAPES - Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior
dc.description.sponsorshipFAPESP - The State of Sao Paulo Research Foundation
dc.description.sponsorshipIDCAPES: 1067/10
dc.description.sponsorshipIDFAPESP: 2015/10109-5
dc.description.sponsorshipIDFAPESP: 2015/18125-0
dc.format.extent386-398
dc.identifierhttp://dx.doi.org/10.2174/1567205014666171016101816
dc.identifier.citationCurrent Alzheimer Research. Sharjah, v. 15, n. 4, p. 386-398, 2018.
dc.identifier.doi10.2174/1567205014666171016101816
dc.identifier.fileWOS000426616800009.pdf
dc.identifier.issn1567-2050
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/53845
dc.identifier.wosWOS:000426616800009
dc.language.isoeng
dc.publisherBentham Science Publ Ltd
dc.relation.ispartofCurrent Alzheimer Research
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectAlzheimer diseaseen
dc.subjectdementiaen
dc.subjectdrug therapyen
dc.subjectneurodegenerative diseasesen
dc.subjectneuropsychiatryen
dc.subjectpharmacogeneticsen
dc.subjectrenin-angiotensin systemen
dc.titlePharmacogenetics of Angiotensin-Converting Enzyme Inhibitors in Patients with Alzheimer's Disease Dementiaen
dc.typeinfo:eu-repo/semantics/article
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