O POTENCIAL FARMACOGENÉTICO DA APOLIPROTEINA-E NO TRATAMENTO DA DOENÇA DE ALZHEIMER
CAVALARI, Caroline Maria de Andrade1; NASCIMENTO, Carlos Guilherme3; SIMAO, Daiane Priscila2;
Introdução:The Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cholinergic impairment, memory loss, neurofibrillary tangles and accumulation of ? amyloids plaques. It affects more than 35 million people worldwide. Its occurrence is multifactorial and between the genetic key factors, the allele APO?4 is the most predisposition to the illness. Within the multiple role of Apoliprotein E (APoE) in the organism, it is questioned whether it modulates the activity of butyrylcholinesterase (BChE), target of cholinergic inhibitors, the first line treatment of AD, therefore, your pharmacogenetic potential is tested indirectly.
Objetivo:This study aimed to assess the pharmacogenetic potential of APOE for cholinergic inhibitors (galantamine, rivastigmine and donepezil) prescription for Alzheimer’s disease.
Metodologia:This research was accepted by Ethics Committee and Research of UFPR (n. protocol 1192.117.11.08), and held the participation of 230 volunteers, being 112 AD carriers aligned with gender, age, scholar years with 118 cognitively healthy elders (EC). The statistical analysis of population variances and plasmatic protein profile of APOE, as well as plasmatic BChE activity, were conducted through statistics programs SPPS and Statview.
Resultados:The mean ApoE plasmatic concentration was significantly higher (18.28 ± 8.48µg/mL) for AD than EC group (12.50 ± 4.70µg/mL) (p = 0.00). The genotypic frequency was also significantly different between AD and CI (X2 = 20,63; p = 0.00) with allele APO?4+ frequency as 48.21% for AD and 23.68% for EC, corroborating as a risky factor for AD. Considering only the patients group, it was possible to identify that the concentrations of ApoE significantly differed in terms of phenotype. In the presence of APO?4, the plasmatic concentration of APoE was lower (46.67µg/mL) in comparison to its absence (64.14µg/mL). Whereas the APO?2+ allele showed a higher concentration of ApoE in its presence (79.11µg/mL) than its lack (49.91µg/mL). Verifying the BChE protein activity, one of the cholinesterase inhibitors target, considering their usage or not, there was only difference in the activity of those patients who did not use them, and had, at least, one APO?2+ allele. While those with APO?4+ allele had lower (17.91µg/ml) concentration than APO?4- (25.91µg/ml). Both cholinesterases, AChE and BChE, have their activity affected by numerous homeostatic factors, among them the interaction with ApoE. In this way, an evaluation of the pharmacogenomic potential of ApoE in its evaluation through the enzymatic activity of BChE evaluated only one of the elements that can be altered with the use of the inhibitors, being necessary an amplification of the variables to better understand the dynamics of this process.
Conclusões:The fact that the plasma concentration levels of ApoE differ in their APO?2 +/- and APO?4 +/- variant forms only among patients who were not using the IChEs, point out that the use of inhibitors affected the protein concentration of ApoE. This indicates a possible effect of the drugs under the same concentration, which justifies the need to conduct studies by amplifying the variables under analysis, aiming at a better understanding of these interactions and their pharmacogenetic role.
Palavras-chave:Butyrylcholinesterase. Cholinergic inhibitors. Apoliprotein E.