title: Analysis of functional polymorphisms in three synaptic plasticity-related genes (BDNF, COMT AND UCHL1) in Alzheimer's disease in Colombia.
abstract: In recent years, it has been proposed that synaptic dysfunction may be an important etiological factor for Alzheimer's disease (AD). This hypothesis has important implications for the analysis of AD genetic risk in case-control studies. In the present work, we analyzed common functional polymorphisms in three synaptic plasticity-related genes (brain-derived neurotrophic factor, BDNF Val66Met; catechol-O-methyl transferase, COMT Val158; ubiquitin carboxyl-terminal hydroxylase, UCHL1 S18Y) in a sample of 102 AD cases and 168 age and sex matched controls living in Bogotá, Colombia. There was not association between UCHL1 polymorphism and AD in our sample. We have found an initial association with BDNF polymorphism in familial cases and with COMT polymorphism in male and sporadic patients. These initial associations were lost after Bonferroni correction for multiple testing. Unadjusted results may be compatible with the expected functional effect of variations in these genes on pathological memory and cognitive dysfunction, as has been implicated in animal and cell models and also from neuropsychological analysis of normal subjects carriers of the AD associated genotypes. An exploration of functional variants in these and in other synaptic plasticity-related genes (a synaptogenomics approach) in independent larger samples will be important to discover new genes associated with AD.
authors.affiliation: Grupo de Neurociencias, Facultad de Medicina e Instituto de Genética, Universidad Nacional de Colombia, Bogotá, Colombia.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Forero
authors.forename: Bruno
authors.initials: B
authors.lastname: Benítez
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Arboleda
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Yunis
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Pardo
authors.forename: Humberto
authors.initials: H
authors.lastname: Arboleda
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D001923:Brain Chemistry / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D015331:Cohort Studies; D003105:Colombia; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009416:Nerve Regeneration / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D020127:Recovery of Function / Q000235:genetics; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005819:Genetic Markers; C482860:UCHL1 protein, human; D002394:Catechol O-Methyltransferase; D043222:Ubiquitin Thiolesterase