Dataset Information

Pharmacogenetic analyses of variations of measures of cardiovascular risk in Alzheimer's dementia.

ABSTRACT: Background & objectives:Neurodegeneration affects blood pressure variations, while renal function and cerebral perfusion are impaired by vascular risk factors. This study was aimed to estimate variations of measures of cardiovascular risk in Alzheimer's dementia by pharmacogenetic analyses of the effects of angiotensin-converting enzyme (ACE) inhibitors and statins. Methods:Consecutive patients were prospectively followed to study variations of creatinine clearance and blood pressure for one year, estimated by correlating the effects of ACE inhibitors with the ACE Alu I/D polymorphism and genotypes or haplotypes of rs1800764 or rs4291, and the effects of statins with LDLR (low-density lipoprotein receptor) genotypes or haplotypes of rs11669576 (exon 8) or rs5930 (exon 10), or genotypes of rs2695121 (liver X receptor ? gene). Variations of the coronary heart disease (CHD) risk according to these cardiovascular measures were also explored. Results:All polymorphisms of the 193 patients were in Hardy-Weinberg equilibrium. Genetic determinants of cardiovascular effects affected the individual variability of the response to ACE inhibitors and statins. ACE inhibitors, but not statins, reduced blood pressure for all patients. ACE inhibitors protected carriers of alleles that supposedly decrease serum ACE levels (rs1800764-T, rs4291-A, Alu II) regarding creatinine clearance variations (P <0.005), but carriers of Alu DD (P <0.02), rs1800764-C (P <0.05), or rs4291-AT (P <0.04) showed better blood pressure lowering effects. The presence of rs2695121-T (P=0.007) or rs5930-A (P=0.039) was associated with systolic blood pressure lowering, whereas rs5930-AA was protective against decrease in creatinine clearance (P=0.019). Statins lowered creatinine clearance for carriers of rs2695121-CT (P=0.026). Interpretation & conclusions:Pharmacological response of blood pressure and creatinine clearance to ACE inhibitors and statins may be genetically mediated.

SUBMITTER: de Oliveira FF

PROVIDER: S-EPMC6886147 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pharmacogenetic analyses of variations of measures of cardiovascular risk in Alzheimer's dementia.

de Oliveira Fabricio Ferreira FF Berretta Juliana Marília JM de Almeida Junior Guido Veiga GV de Almeida Sandro Soares SS Chen Elizabeth Suchi ES Smith Marilia Cardoso MC Bertolucci Paulo Henrique Ferreira PHF

The Indian journal of medical research 20190901 3

<h4>Background & objectives</h4>Neurodegeneration affects blood pressure variations, while renal function and cerebral perfusion are impaired by vascular risk factors. This study was aimed to estimate variations of measures of cardiovascular risk in Alzheimer's dementia by pharmacogenetic analyses of the effects of angiotensin-converting enzyme (ACE) inhibitors and statins.<h4>Methods</h4>Consecutive patients were prospectively followed to study variations of creatinine clearance and blood press ...[more]

PMID: 31719297

Similar Datasets

Project description:ObjectivesThe association between gout and dementia, Alzheimer's disease (AD), or vascular dementia (VD) is not fully understood. The aim of this meta-analysis was to evaluate the risk of all-cause dementia, AD, and VD in gout patients with or without medication.MethodsData sources were PubMed, Embase, the Cochrane Library, and reference lists of included studies. This meta-analysis included cohort studies assessing whether the risk of all-cause dementia, AD, and VD was associated with gout. The risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to access the overall certainty of evidence. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a random-effects model, and publication bias was assessed with funnel plots and Egger's test.ResultsA total of six cohort studies involving 2,349,605 individuals were included in this meta-analysis, which were published between 2015 and 2022. The pooling analysis shows that the risk of all-cause dementia was decreased in gout patients [RR = 0.67, 95% CI (0.51, 0.89), I2 = 99%, P = 0.005, very low quality], especially in gout patients with medication [RR = 0.50, 95% CI (0.31, 0.79), I2 = 93%, P = 0.003, low quality]. The risk of AD [RR = 0.70, 95% CI (0.63, 0.79), I2 = 57.2%, P = 0.000, very low quality] and VD [RR = 0.68, 95% CI (0.49, 0.95), I2 = 91.2%, P = 0.025, very low quality] was also decreased in gout patients. Despite the large heterogeneity, the sensitivity analysis indicated that the results were robust, and there was little evidence of publication bias.ConclusionThe risk of all-cause dementia, AD, and VD is decreased in gout patients, but the quality of evidence is generally low. More studies are still needed to validate and explore the mechanisms of this association.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42022353312.

Dataset Information

Pharmacogenetic analyses of variations of measures of cardiovascular risk in Alzheimer's dementia.

Publications

Pharmacogenetic analyses of variations of measures of cardiovascular risk in Alzheimer's dementia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets