RESUMO
It is shown that Notch 4 plays important roles in the pathogenesis of Alzheimer's disease (AD). To investigate whether three single nucleotide polymorphisms (SNPs) of the Notch4 gene are associated with AD, the three SNPs were genotyped by a polymerase chain reaction-restriction fragment length polymorphism method for 243 AD patients and 130 age-matched controls. We also confirmed the linkage disequilibrium among these three SNPs of the gene using the EH program. The three SNPs did not seem to alter risk for AD. Our study suggests that SNPs studied are not associated with AD. The linkage disequilibrium of this locus indicates that there is genetic heterogeneity in the Notch4 gene. We could not confirm the previous synergetic associations of the 5' untranslated region (rs367398) C/C genotype in apolipoprotein E epsilon4 bearers in AD patients. Potential markers nearby the 5' untranslated region polymorphism might affect risk for AD.
Assuntos
Doença de Alzheimer/genética , Povo Asiático/genética , Polimorfismo Genético , Proteínas Proto-Oncogênicas/genética , Receptores Notch/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Feminino , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptor Notch4RESUMO
To investigate the effect of single nucleotide polymorphisms (SNPs) of the upstream stimulatory factor (USF) 1 and 2 genes on the onset of Alzheimer's disease (AD), a case-control study was performed. The SNPs were genotyped by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 236 AD patients and 120 age-matched controls of Japanese descent. We observed no significant association between the three SNPs of the USF 1 gene and AD in our Japanese participants. In addition, the SNPs studied did not affect plasma cholesterol levels in our AD cases. For the USF 2 gene, the two SNPs did not show significant association with onset of AD. Our study suggests that the three SNPs of the USF 1 gene and two SNPs of the USF 2 gene presented here are not associated with onset of AD.
Assuntos
Doença de Alzheimer/genética , Polimorfismo de Nucleotídeo Único , Fatores Estimuladores Upstream/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Genótipo , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Estatísticas não ParamétricasRESUMO
Disturbed glutamatergic neurotransmission, especially disturbed N-methyl-D-aspartate (NMDA) receptor function, has been hypothesized to be involved in the pathophysiology of schizophrenia. It may also involve abnormalities in the intracellular signaling machineries that are linked to the NMDA receptor. Postsynaptic density-95 is known to bind NMDA receptor subunits and is involved in intracellular signal transduction and synaptic plasticity. Recently, we reported that gene expression of postsynaptic density-95 was altered in schizophrenic brains compared to controls. Therefore, in this study, we examined six polymorphisms in and around the postsynaptic density-95 gene in 259 schizophrenic cases and 188 healthy controls using TaqMan technology. The results suggested that these six polymorphisms did not affect risk for schizophrenia.
