RESUMEN
Presenilin 1 (PSEN1) and presenilin 2 (PSEN2) genes encode the major component of y-secretase, which is responsible for sequential proteolytic cleavages of amyloid precursor proteins and the subsequent formation of amyloid-ß peptides. 150 RNA samples from the entorhinal cortex, auditory cortex and hippocampal regions of individuals with Alzheimer's disease (AD) and controls elderly subjects were analyzed with using real-time rtPCR. There were no differences between groups for PSEN1 expression. PSEN2 was significantly downregulated in the auditory cortex of AD patients when compared to controls and when compared to other brain regions of the patients. Alteration in PSEN2 expression may be a risk factor for AD.
Asunto(s)
Enfermedad de Alzheimer/patología , Encéfalo/metabolismo , Presenilina-1/genética , Presenilina-2/genética , Anciano , Anciano de 80 o más Años , Proteínas de Arabidopsis/metabolismo , Encéfalo/patología , Femenino , Regulación de la Expresión Génica/fisiología , Humanos , Transferasas Intramoleculares/metabolismo , Masculino , Presenilina-1/metabolismo , Presenilina-2/metabolismoRESUMEN
Alzheimer's disease (AD) is a progressive neurodegenerative disease that takes the form of a local overexpression of cytokines and other inflammatory molecules. We investigated three single-nucleotide polymorphisms (SNP) of the interleukin 6 gene (IL-6) promoter region [-174G/C (rs 1800795), -572C/G (rs 1800796), and -597G/A (rs 1800797)] in 200 patients with late-onset AD and 165 elderly controls in a Brazilian case-control population sample. Genotyping was carried out from blood cells using PCR-RFLP techniques. Statistical analysis was performed to evaluate the Hardy-Weinberg equilibrium and to compare frequencies between groups. No association was found between any IL-6 polymorphism and AD; however the haplotype composed of the -597 A allele and the -174G allele indicated a crude odds ratio (OR) of 0.15 (p = 0.0021) and a significantly adjusted OR (adjusted for the APOE E4 allele value) of 0.15 (p = 0.00294). Linkage disequilibrium was D' = 0.68 among the three SNPs. Our findings revealed a protective effect of AG (-597A, -174G) haplotype, which worked independently of the APOE E4 allele in our Brazilian population sample. Thus, the promoter region of IL-6 gene probably exerts an effect through gene linkage and/or gene interaction.
Asunto(s)
Alelos , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/genética , Estudios de Asociación Genética/métodos , Haplotipos/genética , Interleucina-6/genética , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Brasil/epidemiología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Our study aimed to associate IL-1ß and IL-1RN polymorphisms with AD disease in comparison with elderly control group from São Paulo - Brazil. We genotyped 199 Alzheimer's disease (AD) patients, 165 elderly control and 122 young control samples, concerning VNTR (IL-1RN) and -511C>T and -31T>C (IL-1ß) polymorphisms. Our findings revealed that -511C/-31T/2-repetitions VNTR haplotype had a protective effect for AD when compared to EC (p=0.005), whereas -511C/-31C/1-repetition VNTR haplotype was associated as a risk factor for AD (p=0.021). Taken together, we may suggest that there is a relevant role of IL-1 genes cluster in AD pathogenesis in this Brazilian population.