RESUMEN
Based on the pathophysiological role of adenosine A(2A) receptors in HD, we have evaluated the association of the 1976C/T single-nucleotide polymorphism in the ADORA2A gene (rs5751876) with residual age at onset (AAO) in HD. The study population consisted of 791 unrelated patients belonging to the Huntington French Speaking Network. The variability in AAO attributable to the CAG repeats number was calculated by linear regression using the log (AAO) as the dependent variable, and the respective rs5751876 genotypes as independent variables. We show that the rs5751876 variant significantly influences the variability in AAO. The R(2) statistic rose slightly but significantly (p=0.019) when rs5751876 T/T genotype was added to the regression model. Patients harbouring T/T genotype have an earlier AAO of 3.8 years as compared to C/C genotype (p=0.02). Our data thus strengthens the pathophysiological role of A(2A) receptors in Huntington's disease.
Asunto(s)
Enfermedad de Huntington/epidemiología , Enfermedad de Huntington/genética , Polimorfismo de Nucleótido Simple , Receptor de Adenosina A2A/genética , Adolescente , Adulto , Edad de Inicio , Anciano , Niño , Estudios de Cohortes , Genotipo , Humanos , Modelos Lineales , Persona de Mediana Edad , Expansión de Repetición de Trinucleótido , Adulto JovenRESUMEN
The transport of amyloid precursor protein is mediated through its interaction with kinesin light-chain 1 (KNS2). We hypothesized that kinesin light-chain dysfunction might be involved in the pathogenesis of Alzheimer's disease (AD). To assess the physiological relevance of an allelic variation in the KNS2 gene, the association analysis of three single nucleotide polymorphisms (SNPs) in the 5'UTR or in intronic sequences of KNS2 gene were performed in 100 AD brain patients and in 103 controls. For one of these polymorphisms (G58836C in intron 13), the association between AD and the C allele was found to be significant (odds ratio = 1.73, 95% CI: 1.12-2.67, P = 0.012). No synergistic effects were found between the APOE epsilon 4 allele and KNS2 gene polymorphisms.