RESUMEN
Levodopa-induced dyskinesia (LID) is an adverse effect that negatively impacts the quality of life of patients with Parkinson's disease (PD). Studies report that genetic variations in the genes of the pharmacogenetic pathway of the levodopa (L-DOPA) might be associated with LID development. The goal of the present study was to investigate a possible influence of functional genetic variants in the DRD1 (rs4532), DRD2 (rs1800497), DAT1 (rs28363170), and COMT (rs4680) genes with LID development. A total of 220 patients with idiopathic PD were enrolled. The genotyping for DRD1 (rs4532), DRD2 (rs1800497), DAT1 (rs28363170), and COMT (rs4680) polymorphisms were performed using Restriction Fragment Length Polymorphism (PCR-RFLP). Univariate and multivariate analyses were performed to assess the association of these polymorphisms and risk factors with LID development. Multivariate Cox regression analysis showed increased risk to LID development for both Levodopa Dose Equivalency (LED) (Hazard ratios (HR) = 1.001; 95% CI 1.00-1.01; p = 0.009) and individuals carrying the COMT L/L genotype (HR = 2.974; 95% CI 1.12-7.83; p = 0.010). Furthermore, when performed a Cox regression analysis adjusted for a total LED, we observed that the genotype COMT L/L had a 3.84-fold increased risk for LID development (HR = 3.841; 95% CI 1.29-11.37; p = 0.012). Our results suggest that before treating LID in PD patients, it is important to take into consideration genetic variant in the COMT gene, since COMT LL genotype may increase the risk for LID development.
Asunto(s)
Discinesias/genética , Levodopa/efectos adversos , Enfermedad de Parkinson/tratamiento farmacológico , Farmacogenética/métodos , Polimorfismo de Nucleótido Simple , Catecol O-Metiltransferasa/genética , Estudios de Cohortes , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Discinesias/etiología , Femenino , Genotipo , Humanos , Estimación de Kaplan-Meier , Levodopa/uso terapéutico , Masculino , Receptores de Dopamina D1/genética , Receptores de Dopamina D2/genéticaRESUMEN
Pmp-22 mutant mice (Trembler-J: B6.D2-Pmp22
Asunto(s)
Enfermedad de Charcot-Marie-Tooth/diagnóstico , Evaluación de la Discapacidad , Suspensión Trasera/métodos , Fenotipo , Factores de Edad , Animales , Enfermedad de Charcot-Marie-Tooth/genética , Modelos Animales de Enfermedad , Discinesias/diagnóstico , Discinesias/genética , Diagnóstico Precoz , Femenino , Tamización de Portadores Genéticos/métodos , Heterocigoto , Masculino , Ratones , Ratones Mutantes , Proteínas de la Mielina/genética , Análisis de Secuencia de ADN , Cola (estructura animal)RESUMEN
Type II methemoglobinemia is a somatic deficiency of cytochrome b5 reductase with severe global neurologic impairment. We report a novel mutation in exon 3 of the CYB5R3 gene on chromosome 22 consisting of homozygous 1-base pair (bp) deletion noted as c.215delG; p.Gly72AlafsX100. The patient had improvement of gross motor skills, chewing, and swallowing that may be due to the initiation of daily ascorbic acid therapy. We hypothesize that a possible response to ascorbic acid may be related to the effect of making additional ferrous iron available for its role as a cofactor in carnitine synthesis.