RESUMO
Alzheimer's disease (AD) is the leading cause of dementia. Several studies indicate a possible relationship between different genes and Alzheimer's disease. To further investigate, we have analyzed the association between the bleomycin hydrolase (BLMH) and apolipoprotein E (ApoE) polymorphisms in 93 AD patients and age- and sex-matched 113 controls from the Tunisian population. The frequency of ApoE epsilon 4 allele was found to differ significantly in AD patients compared to the control [29.5% vs. 8.8 (χ (2) = 26, df = 1, p < 0.001)] leading to an increased risk of AD in subjects with this allele (OR = 3.29, 95% CI = 1.7-6.5; p = 0.001]. This risk was found to decrease from OR = 8.4, CI = 3.3-23; p < 0.001 in subjects less than 75 years old to OR = 1.2, CI = 1.031-14; p = 0.0297 in subjects 75 years and older. No association was observed between carrying the BLMH-G genotype and AD in ε4 negative or positive subjects.
Assuntos
Doença de Alzheimer/enzimologia , Doença de Alzheimer/genética , Apolipoproteínas E/genética , Cisteína Endopeptidases/genética , Predisposição Genética para Doença/genética , Polimorfismo Genético/genética , Idoso , Idoso de 80 Anos ou mais , Apolipoproteína E4/genética , Feminino , Triagem de Portadores Genéticos , Humanos , Masculino , TunísiaRESUMO
Recent evidences indicate that polymorphisms within the promoter region of the vascular endothelial growth factor (VEGF) gene may elevate the risk for Alzheimer's disease (AD). To further investigate, we have analyzed association between promoter polymorphisms of the VEGF gene in 93 AD patients and age and sex matched 113 controls from Tunisian population. The distribution of genotype and allele frequencies of the VEGF (-2578C/A) and (-1154G/A) polymorphisms did not differ significantly between AD and control groups (p>0.05). In the subgroup of ApoE varepsilon4 carriers, the -2578A was observed to be significantly higher in the AD patients than in the control individuals. After adjusting the data by gender, age and the ApoE varepsilon4 status using logistic regression, the -2578A allele was found to increase the risk for sporadic AD by 1.7-fold. The present study provides the evidence that the -2578A allele may be associated with the development of AD in the individuals with ApoE varepsilon4 allele. In addition, AD patients carrying the -2578A allele had lower Abeta42 (p=0.029) levels than those without this allele, particularly in subjects with ApoE varepsilon4 allele.
Assuntos
Doença de Alzheimer/genética , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano , Fator A de Crescimento do Endotélio Vascular/genética , Proteínas tau/líquido cefalorraquidiano , Idade de Início , Idoso , Doença de Alzheimer/metabolismo , Apolipoproteína E4/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Polimorfismo Genético , Regiões Promotoras Genéticas , TunísiaRESUMO
There is substantial evidence found in the literature that supports the fact that the presence of oxidative stress may play an important role in the physiopathology of schizophrenia. Previous studies have reported the occurrence of impairments in the glutathione levels and the activities of the antioxidant enzymes in patients suffering from schizophrenia. However, most of these studies were performed on treated patients. The present study evaluated treated schizophrenic patients (n=52) along with neuroleptic-free or untreated schizophrenic patients (n=36) and healthy controls (n=46). The blood glutathione levels: total glutathione (GSHt), reduced glutathione (GSHr), and oxidized glutathione (GSSG) as well as the activities of the antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were measured. The psychopathology of the patients was assessed through the Clinical Global Impressions-severity (CGI-severity). The tests revealed that in comparison with the healthy controls, the schizophrenic patients showed significantly lower levels of GSHr, SOD, and CAT. Among the schizophrenic patients, the activities of the antioxidant enzymes SOD and CAT were recorded to be significantly lower in untreated patients than in the treated ones. In addition, the levels of both GSHt and GSHr were found to be inversely correlated with the obtained CGI-severity score. These results evidently suggest that a decrease in the glutathione levels and the activities of the antioxidant enzymes in patients diagnosed with schizophrenia is not related to neuroleptic treatment and could be considered as a biological indicator of the degree of severity of the symptoms of schizophrenia.