RESUMEN
BACKGROUND: Apolipoprotein E expression is increased in regenerating neural tissue and the APOE epsilon4 allele is associated with impaired neuronal repair. Since repair is essential for the restoration of central nervous system function following multiple sclerosis (MS) relapses, APOE genotype may influence clinical progression of the disease. OBJECTIVE: To examine the association of the APOE genotype with disease susceptibility and progression in MS. PATIENTS AND METHODS: APOE genotyping was determined by polymerase chain reaction and restriction enzyme digestion in 47 patients with MS who had been followed up every 3 months for 2 years as part of an open-label clinical trial with glatiramer acetate. The Expanded Disability Status Scale (EDSS) was used to assess clinical progression. RESULTS: Nine patients were heterozygous and 1 patient was homozygous for the APOE epsilon4 allele, for a frequency of 12% (11/94), which is similar to that of the general Israeli population. The APOE epsilon4 carriers had a mean +/- SE EDSS score of 3.10+/-0.45 at entry, which was not significantly different from the remaining 37 patients (2.62+/-0.25). During the observation period, the EDSS score of the APOE epsilon4 carriers deteriorated to 4.00+/-0.63 while the other patients remained stable with an EDSS score of 2.74+/-0.31. The interaction of genotype with disability over time was significant (P = .02 by repeated-measures analysis of variance). There were no differences in the number of relapses occurring in the 2 groups. CONCLUSIONS: These preliminary observations suggest that APOE genotype may influence disease progression in MS. The APOE epsilon4 allele was not associated with an increased risk of MS or relapses.
Asunto(s)
Apolipoproteínas E/genética , Evaluación de la Discapacidad , Esclerosis Múltiple Recurrente-Remitente/genética , Esclerosis Múltiple Recurrente-Remitente/rehabilitación , Adulto , Alelos , Apolipoproteína E4 , Progresión de la Enfermedad , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Proyectos Piloto , Valor Predictivo de las Pruebas , PronósticoRESUMEN
BACKGROUND AND PURPOSE: The alanine/valine (A/V) polymorphism at codon 677 of the 5,10 methylenetetrahydrofolate reductase (MTHFR) gene correlates with elevated levels of plasma homocysteine and with an increased risk of atherosclerotic cardiovascular disease. Our study was designed to assess the frequency of the A and V alleles in patients with asymptomatic severe carotid artery stenosis (CAS) assessed by extracranial duplex examination in comparison with age- and sex-matched subjects without carotid atherosclerosis. METHODS: Consecutive patients (n=48; 28 men, mean+/-SD age 67.1+/-11. 4 years) with asymptomatic severe (>75%) CAS were compared with subjects without CAS (n=26; 15 men, aged 61.2+/-11.5). The MTHFR genotype was analyzed by polymerase chain reaction followed by HinfI digestion. The chi(2) analysis and t test were used to compare the groups. RESULTS: The frequency of V alleles was significantly higher in the CAS group (0.47) compared with control subjects (0.27, chi(2) test; OR 2.4 [95% CI 1.1 to 5.3]; P<0.02). CONCLUSIONS: Our results indicate that the MTHFR A677V allele is significantly associated with severe CAS.