RESUMEN
BACKGROUND: Acetylcholinesterase inhibitors (AChEIs) are the treatment of choice for patients with Alzheimer's disease (AD). However, their efficacy is moderate and differs from patient to patient. Recent studies suggest that the Q192R variant of the paraoxonase 1 gene (PON1) might affect individual susceptibility to these drugs. METHODS: We investigated the influence of 3 single nucleotide polymorphisms (SNPs) in PON1 (rs 662, rs 854560, rs 705381) and the APOE common polymorphism in 101 Polish patients with late-onset AD in response to treatment with AChEIs. RESULTS: No significant differences were observed between carriers and non-carriers of the PON1 SNPs or the APOE common polymorphism in terms of treatment response. These results did not change after stratification of APOE status. CONCLUSION: Our results suggest that both the investigated PON1 and APOE common SNPs do not influence treatment response to AChEIs in patients with AD.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Arildialquilfosfatasa/genética , Anciano , Apolipoproteínas E/genética , Inhibidores de la Colinesterasa/uso terapéutico , ADN/genética , Donepezilo , Femenino , Haplotipos , Heterocigoto , Humanos , Indanos/uso terapéutico , Masculino , Pruebas Neuropsicológicas , Fenilcarbamatos/uso terapéutico , Piperidinas/uso terapéutico , Polimorfismo Genético/genética , Polimorfismo de Nucleótido Simple , Reacción en Cadena en Tiempo Real de la Polimerasa , RivastigminaRESUMEN
BACKGROUND: The relationship between different paraoxonase (PON) gene polymorphisms and the risk of Alzheimer's disease (AD) was studied several times and the results were controversial. METHODS: We investigated the association of 4 single-nucleotide polymorphisms (SNPs) of the PON1 (M55L; Q192R; -161C/T) and the PON2 (C311S) genes that were shown to affect the risk of sporadic AD. We studied 360 Caucasian cases with late-onset AD and 354 nondemented controls. RESULTS: No significant differences were observed between the studied PON SNPs and AD risk. The results did not change after stratification of the apolipoprotein E status. Meta-analyses of studies in Caucasians assessing the associations between the PON1 M55L, -161C/T and Q192R SNPs and the risk of AD were performed, and no associations were found. CONCLUSION: Our results suggest that the studied PON1 and PON2 polymorphisms are not associated with late-onset AD.
Asunto(s)
Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/genética , Arildialquilfosfatasa/genética , Polimorfismo Genético/genética , Factores de Edad , Edad de Inicio , Anciano , Alelos , Apolipoproteínas E/genética , ADN/genética , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , Desequilibrio de Ligamiento , Masculino , Polonia/epidemiología , Polimorfismo de Nucleótido Simple , Población , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Regresión , Factores de Riesgo , Factores SexualesRESUMEN
Interleukin-1 is a potent proinflammatory cytokine involved in the pathophysiology of Alzheimer's disease (AD). We genotyped IL-1beta (-511 C/T) and the apolipoprotein E (APOE) common polymorphisms in a large case-controlled study in a Polish population. We included 332 patients with late-onset AD and 220 controls without any neurological deficit, cognitive complaints and history of neurological diseases, aged > or = 65 years. The distribution of the IL-1beta (-511 C/T) genotypes was similar to that in the controls (AD: C/C = 45.8%, C/T = 44.6%, T/T = 9.6% vs. controls: C/C = 53.9%, C/T = 38.3%, T/T = 7.3%, p > 0.05). Our study confirms previous reports that APOE epsilon4 is strongly related to the risk of AD (odds ratio = 6.60, 95% confidence interval 4.19-10.41). APOE status did not affect the distribution of the studied IL-1beta polymorphism. The IL-1beta (-511 C/T) polymorphism is not a risk factor for late-onset AD in a Polish population.