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

Author(s)

de Oliveira, Fabricio Ferreira ^[1] ; Berretta, Juliana Marilia ^[2] ; de Almeida Junior, Guido Veiga ^[3] ; de Almeida, Sandro Soares ^[4] ; Chen, Elizabeth Suchi ^[5] ; Smith, Marilia Cardoso ^[5] ; Ferreira Bertolucci, Paulo Henrique ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Neurol & Neurosurg, Rua Botucatu 740, BR-04023900 Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Escola Paulista Med, Dept Med, Sao Paulo, SP - Brazil

^[3] Univ Mogi das Cruzes, Mogi Das Cruzes, SP - Brazil

^[4] Univ Fed Sao Paulo, Escola Paulista Med, Dept Biophys, Sao Paulo, SP - Brazil

^[5] Univ Fed Sao Paulo, Escola Paulista Med, Dept Morphol & Genet, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: INDIAN JOURNAL OF MEDICAL RESEARCH; v. 150, n. 3, p. 261-271, SEP 2019.
• Web of Science Citations: 0

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 beta 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. (AU)

• FAPESP's process: 15/10109-5 - Comparative analysis of cerebrospinal fluid and serum markers in dementia with Lewy Bodies and Alzheimer's Disease dementia
• Grantee: Fabricio Ferreira de Oliveira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral