RESUMEN
Different studies have attempted to find polymorphisms involved in the serotonergic pathway that could be involved in mood disorders and late-onset Alzheimer's disease (LOAD) symptoms. Here, we compared the frequency of two polymorphisms: monoamine oxidase A (MAOA) and serotonin transporter in LOAD patients versus controls. No evidence of association was observed when these polymorphisms were compared separately; however, the combination of the MAOA allele 1+the short allele of 5-HTTLPR+ApoE-epsilon4 was significantly more frequent in patients than in controls. It reinforces the hypothesis that different genes acting together might play a role in AD susceptibility. Based on these data, we suggest replicating these studies in larger samples of LOAD patients belonging to different ethnic groups.
Asunto(s)
Enfermedad de Alzheimer/enzimología , Enfermedad de Alzheimer/genética , Monoaminooxidasa/genética , Polimorfismo Genético , Anciano , Enfermedad de Alzheimer/fisiopatología , Apolipoproteínas E/genética , Brasil , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genéticaRESUMEN
After the identification of the apolipoprotein E gene isoform (APOE-epsilon4) as a risk factor for late-onset Alzheimer's disease (LOAD), the search for other polymorphisms associated with AD has been undertaken by many groups of investigators around the world. These studies have shown controversial results in many populations. More recently, a single nucleotide polymorphism in the promoter region of the brain-derived neurotrophin factor (BDNF) was found to be a risk factor for AD in two independent population studies. Here we report the analysis of this polymorphism in a group of 188 LOAD Brazilian patients compared to matched normal controls. A strong association between the APOE-epsilon4 polymorphism and LOAD was observed, but there was no significant association between this BNDF polymorphism and affected patients. The possibility that other polymorphisms or mutations in this gene play a role in the development of AD cannot be ruled out. However, the results of the present study suggest that in opposition to the two reported studies, this polymorphism does not seem to be implicated in LOAD Brazilian patients. It also shows the importance of replication studies in different populations, as susceptibility loci might differ in different ethnic groups; this will have important implications in future treatments with pharmacological agents.