RESUMEN
A recent study identified a polymorphism (Pro86Leu) in the Calcium homeostasis modulator 1 (CALHM1) gene whose minor Leucine allele showed a higher frequency in Alzheimer's disease (AD) patients compared to controls (29% in AD and 22% in controls). Further studies provided conflicting results in different ethnic groups. In order to assess the involvement of the CALHM1 genetic variant on the risk of developing AD, we analyzed the genotype and allele distributions of the Pro86Leu polymorphism in 758 Italian subjects. Our results did not confirm an association between the CALHM1 variation and AD, thus suggesting a genetic heterogeneity among the various populations.
Asunto(s)
Enfermedad de Alzheimer/genética , Canales de Calcio/genética , Leucina/genética , Glicoproteínas de Membrana/genética , Polimorfismo de Nucleótido Simple/genética , Prolina/genética , Edad de Inicio , Anciano , Enfermedad de Alzheimer/clasificación , Análisis Mutacional de ADN/métodos , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Italia , Masculino , Persona de Mediana EdadRESUMEN
A common polymorphism (rs2373115) in the GRB-associated binding protein 2 (GAB2) gene has been recently associated with the risk of developing Alzheimer's disease (AD) in 644 apolipoprotein E (ApoE) epsilon4 carriers. In order to assess the involvement of the GAB2 polymorphism in the risk of developing AD, we analyzed the genotype and allele distributions of the GAB2 rs2373115 polymorphism in 579 Italian subjects. Our results support a possible implication of GAB2 genetic variant in AD. However, the observed association was confined to ApoE epsilon4 non-carriers, thus suggesting a possible role of GAB2 as an independent risk factor for AD.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Enfermedad de Alzheimer/genética , Polimorfismo Genético , Enfermedad de Alzheimer/epidemiología , Apolipoproteínas E/genética , Predisposición Genética a la Enfermedad/epidemiología , Genotipo , Humanos , Italia/epidemiología , Factores de RiesgoRESUMEN
Recent studies have reported a genetic association between the 73 G/A polymorphism within exon 1 of the cystatin C gene and Alzheimer's disease (AD) with conflicting results. To further investigate the proposed association and to clarify the role of CST3 as risk factor for AD, we analyzed the genotype and allele frequency distribution of CST3 G73A and apolipoprotein (ApoE) gene polymorphisms in 243 Italian patients with AD and 186 controls. Patients with AD were consecutively collected among the outpatients from the Neurology Department at the University of Florence. All 429 subjects were genotyped for CST3 and ApoE polymorphisms. After stratification according to age, the GG frequency resulted slightly higher in younger (<65 years) cases, but far from statistically significant. There was also no evidence of a statistical interaction between CST3 and ApoE polymorphisms. In conclusion, our data suggest that the CST3 genetic variant is not a susceptibility factor in AD, nor mitigate the effect of the ApoE varepsilon4 allele in the risk of developing AD.
Asunto(s)
Enfermedad de Alzheimer/genética , Apolipoproteínas E/genética , Cistatinas/genética , Polimorfismo Genético , Anciano , Enfermedad de Alzheimer/epidemiología , Análisis de Varianza , Cistatina C , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Italia/epidemiología , Masculino , ARN Mensajero/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodosRESUMEN
A recent study has shown that a genetic variation in the Cathepsin D (catD) gene is a major risk factor for the development of Alzheimer's disease (AD). CatD is an intracellular aspartyl protease involved in neurodegeneration. A C-->T (Ala-->Val) transition at position 224 has been associated with altered intracellular maturation. Recently, a significant overrepresentation of the T allele of the catD gene in AD patients compared with controls was reported. However, this finding has not yet been confirmed. We analyzed the distribution of catD and apolipoprotein E polymorphisms in Italian patients with sporadic and familial AD (FAD). Our studies revealed that the distribution of catD polymorphism did not differ in AD and FAD patients and controls. Thus, our data do not support a role for the catD gene as a genetic risk factor in the development of AD.