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P2‐025: PHARMACOGENETICS OF CHOLESTEROL‐LOWERING DRUGS IN PATIENTS WITH DEMENTIA DUE TO ALZHEIMER'S DISEASE
Author(s) -
Ferreira de Oliveira Fabricio,
Ferreira Bertolucci Paulo Henrique,
Chen Elizabeth Suchi,
Cardoso Smith Marilia Arruda
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.05.698
Subject(s) - apolipoprotein e , pharmacogenetics , medicine , dementia , haplotype , genotype , genotyping , allele , oncology , endocrinology , gastroenterology , pharmacology , genetics , biology , disease , gene
dementia due to Alzheimer’s disease (AD). Methods: In this pharmacogenetic study, participants with late-onset AD according to National Institute on Aging Alzheimer’s Association criteria were screened with Mini-Mental State Examination (MMSE) and Clinical Dementia Rating Sum-of-Boxes (CDR-SB) and followed for one year. Genotyping was undertaken with TaqMan Real-Time PCR technology for ACE gene polymorphisms rs1800764 and rs4291, and also for APOE. Presence of each polymorphism was correlated with APOE haplotypes and treatment using bpACEis Captopril or Perindopril. Mann-Whitney test and two-way ANOVA were employed for statistics, significance at r<0.05. Results: A total of 184 consecutive patients were included, with minor allele frequencies of 0.49 (rs1800764 C) and 0.33 (rs4291 T). Overall 175 patients (95.1%) used cholinesterase inhibitors, whereas 149 (80.9%) had systemic hypertension, and 112 (60.8%) used bpACEis. Patients with the APOE -ε4/ε4 haplotype had earlier onset of AD (r<0.007), while rs1800764 and rs4291 genotypes had no influence over age of dementia onset (r>0.08), even after controlling for APOE haplotypes (r>0.09). All patients who used bpACEis had slower cognitive decline according to the MMSE (r1⁄40.004), but only those who were APOE4had slower cognitive decline according to CDR-SB scores (r1⁄40.025). Carriers of the rs1800764 TT genotype had slower worsening of CDR-SB scores (r1⁄40.049), particularly when they were APOE4+ (r1⁄40.041). Treatment with bpACEis was particularly effective for slowing the worsening of CDR-SB scores (r1⁄40.017) for carriers of the haplotype rs1800764 CC : rs4291 TT.Conclusions:Captopril and Perindopril may slow the cognitive decline of patients with AD, more remarkably for carriers of specific ACE gene polymorphisms.