RESUMEN
Angiotensin-converting enzyme (ACE) has shown altered activity in patients with neurological diseases. An insertion/deletion (I/D) polymorphism of the ACE gene encoding angiotensin-converting enzyme has been reported to be associated with the risk for Alzheimer's disease (AD), and is generally considered to be a disorder primarily affecting memory. We conducted a case-control study in a sample composed of 85 sporadic AD patients and 90 age- and sex-matched controls to investigate the possible effect of the polymorphism and cognitive profile. Our data revealed an association between the ACE polymorphism and AD risk. There was a significant difference in the ACE allele or genotype frequencies between cases and controls. The D/D genotype showed an increased risk for AD and in the amnestic group and the effect was independent on ApoE genotypes.
Asunto(s)
Enfermedad de Alzheimer/genética , Apolipoproteína E4/genética , Predisposición Genética a la Enfermedad/genética , Peptidil-Dipeptidasa A/genética , Anciano , Alelos , Estudios de Casos y Controles , Cognición , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Polimorfismo de Nucleótido Simple , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , TúnezRESUMEN
A minority of Alzheimer disease (AD) patients begin presenting symptoms before the age of 65 years. A familial aggregation is often found in this group of early-onset AD, and, in a subset of families, the pattern of inheritance is consistent with autosomal dominant inheritance. Fully penetrant variants in amyloid precursor protein, presenilin 1 (PSEN1), and presenilin 2 are the only causative mutations reported for autosomal dominant AD. This study is to explore the PSEN1 gene mutation in a Tunisian familial Alzheimer's disease. The patient in this family showed a novel missense mutation in exon 4 of the PSEN1 gene (complementary DNA 248T>C), altering isoleucine to threonine at 83 position. Because the change occurred in conserved domains of this gene, and cosegregated with affected family member, we suggested that this change may have a mutagenic and probably pathogenic effect.
Asunto(s)
Enfermedad de Alzheimer/genética , Estudios de Asociación Genética , Mutación Missense , Presenilina-1/genética , Anciano , Exones/genética , Femenino , Genes Dominantes/genética , Humanos , Isoleucina/genética , Masculino , Persona de Mediana Edad , Estructura Terciaria de Proteína/genética , Treonina/genética , TúnezRESUMEN
The goal of the study was to examine the Apolipoprotein E (APOE) genotypes in a Tunisian sample of patients with Alzheimer disease (AD) and normal controls, and to compare the results with the findings from the literature. A hospital-based case-control study of two groups (58 patients with AD, 71 controls) was conducted. Patients received a detailed clinical history, neurological examination, neuropsychological testing and brain imaging. A neurological examination and the Arabic version of the Mini-Mental State Examination were made for controls. Genotyping was performed using the PCR restriction fragment length polymorphism (PCR-RFLP) method. There were no statistical differences in age (p = 0.05) and gender (p = 0.046) between the two groups. The APOE ε4/4 genotype was over represented in the AD group in comparison with the controls (13.3 vs. 2.8%). A significant increased risk of AD among APOE ε4 allele carriers was observed. The odds ratio for the association of AD patients with homozygous and heterozygous ε4 allele was, respectively, 5.40 (1.35-21.48) and 2.90 (1.27-6.62). Our results in addition to previously published genetic studies suggest that AD disease is multifactor in origin. Ethnicity, genetic and environmental factors contribute to AD risk in different ethnic groups.