Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo/genética , Moclobemida/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Monoaminoxidase/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Adulto , Idoso , Alelos , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/enzimologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Idiopathic Parkinson's disease (PD) is a common neurodegenerative disorder with prominent motor symptoms. However, depression is common in PD, affecting about 40% of PD patients. Since there is extensive evidence of degeneration of serotonin (5HT) neurons and loss of the 5HT transporter (5HTT) in PD, we assessed whether a functional polymorphism in the promoter of the 5HTT gene (5HTT gene-linked polymorphic region, 5HTTLPR), which determines high or low 5HT uptake, is associated with depressive symptomatology in PD patients. We found that patients with the short allele of the 5HTTLPR had significantly higher scores on the Hamilton Depression Scale. A functional promoter polymorphism of the monoamine oxidase A (MAOA) gene showed no association. Thus, the 5HTTLPR but not the MAOA gene promoter-associated polymorphism may be a risk factor for depression in PD patients, while neither polymorphism increases the risk for development of Parkinson's disease itself.
Assuntos
Proteínas de Transporte/genética , Depressão/genética , Variação Genética , Glicoproteínas de Membrana/genética , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Doença de Parkinson/genética , Alelos , Feminino , Expressão Gênica , Humanos , Masculino , Monoaminoxidase/genética , Doença de Parkinson/psicologia , Polimorfismo Genético , Regiões Promotoras Genéticas/genética , Proteínas da Membrana Plasmática de Transporte de SerotoninaRESUMO
Functional characterization studies revealed that transcriptional activity of the human monoamine oxidase A (MAOA) gene is modulated by a polymorphic repetitive sequence located approximately 1.2 kb upstream of the ATG codon. To investigate the possible influence of the allelic variants of the MAOA gene-linked polymorphic region (MAOA-LPR) on the genetic predisposition to psychiatric disorders, we have performed a case-control association study. 174 patients with affective disorders and 258 patients with schizophrenia according to DSM-IV, as well as 229 population controls were tested. Statistical analysis showed no significant differences in allele or genotype frequencies between control and patient groups. Our results suggest that there is no association between MAOA-LPR genotype and susceptibility to recurrent major depression, bipolar disorder, and schizophrenia in our population.
Assuntos
Transtornos Mentais/genética , Monoaminoxidase/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Adulto , Idade de Início , Alelos , Transtorno Bipolar/genética , Estudos de Casos e Controles , Códon , Depressão/genética , Feminino , Genótipo , Humanos , Íntrons , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/genética , Esquizofrenia/genéticaRESUMO
Various polymorphisms of the X-chromosomal monoamine oxidase A (MAO-A) gene were investigated for association with affective disorders. However, none of the studied variants could consistently be associated with either major depressive or bipolar affective disorder. Recently, a positive association between panic disorder and a novel functional repeat polymorphism in the MAO-A gene promoter, with the longer alleles being more active, was reported. Since monoaminergic neurotransmission is supposed to play an important role in affective disorders, we investigated a potential association of this polymorphism with major depressive illness in a sample of 146 unrelated patients of German descent and a control group of 101 individuals with a negative life history for affective disorders. Similarly to the recent findings in panic disorder, we observed a significantly increased frequency of genotypes containing only long alleles in female patients with recurrent major depression in comparison with age- and sex-matched controls. Thus, our data suggest that an excess of high-activity MAO-A gene promoter alleles resulting in an elevated MAO-A activity is a risk factor for major depressive disorder in females. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:801-803, 2000.
