RESUMO
Brain-derived neurotrophic factor (BDNF) plays an important role in hippocampal synaptic plasticity and long-term potentiation. A valine (Val) to methionine (Met) substitution in the BDNF gene (Val66Met) has been associated with episodic memory performance. This study aimed at fine-mapping the genomic region harbouring BDNF and the adjacent gene, BDNFOS, in order to identify other possible memory-related gene variants. Healthy young Swiss adults (n=333) underwent a verbal memory free-recall task which used words with both neutral and emotional content. Genetic variability of the BDNF and BDNFOS region was covered by analysing 55 single nucleotide polymorphisms (SNPs). Among all examined SNPs, the non-synonymous Val66Met SNP rs6265 showed the highest significant level of association with memory performance for words with emotional content. Recall performance for neutral words was unrelated to the analysed SNPs. Our results support a role for the Val66Met BDNF polymorphism in episodic memory and suggest a modulatory influence of emotional valence.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Mapeamento Cromossômico/métodos , Memória Episódica/fisiologia , Metionina/genética , Polimorfismo de Nucleotídeo Único/genética , Valina/genética , Adolescente , Adulto , Cromossomos Humanos Par 11/genética , Emoções/fisiologia , Feminino , Variação Genética/genética , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The catechol-O-methyltransferase gene (COMT) plays a crucial role in the metabolism of catecholamines in the frontal cortex. A single nucleotide polymorphism (Val(158)Met SNP, rs4680) leads to either methionine (Met) or valine (Val) at codon 158, resulting in a three- to fourfold reduction in COMT activity. The aim of the present study was to assess the COMT Val(158)Met SNP as a risk factor for attention-deficit/hyperactivity disorder (ADHD), ADHD symptom severity and co-morbid conduct disorder (CD) in 166 children with ADHD. The main finding of the present study is that the Met allele of the COMT Val(158)Met SNP was associated with ADHD and increased ADHD symptom severity. No association with co-morbid CD was observed. In addition, ADHD symptom severity and early adverse familial environment were positive predictors of lifetime CD. These findings support previous results implicating COMT in ADHD symptom severity and early adverse familial environment as risk factors for co-morbid CD, emphasizing the need for early intervention to prevent aggressive and maladaptive behavior progressing into CD, reducing the overall severity of the disease burden in children with ADHD.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Catecol O-Metiltransferase/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Adolescente , Alelos , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Criança , Comorbidade , Transtorno da Conduta/epidemiologia , Transtorno da Conduta/genética , Meio Ambiente , Família , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Fatores de Risco , Análise de Sequência de DNARESUMO
A functional polymorphism (His452Tyr) in the gene encoding the serotonin 2A receptor (HTR2A) has been previously associated with human episodic memory performance and with differences in brain volume in memory-related brain regions. Here we present data obtained through imputation and fine-mapping showing that multiple loci within HTR2A are significantly associated with human memory performance independently of the His452Tyr polymorphism. Our data support the existence of multiple memory-related loci within HTR2A.