RESUMEN
Iron overload may lead to neurodegenerative disorders such as Parkinson's disease (PD) and alterations of iron-related genes might be involved in the pathogenesis of this disease. The gene of haemochromatosis (HFE) encodes the HFE protein which interacts with the transferrin receptor (TFR), lowering its affinity for iron-bound transferrin (TF). We examined four known polymorphisms, C282Y and H63D in the HFE gene, G258S in the TF gene and S82G in the TFR gene, in 181 sporadic PD patients and 180 controls from Southern Italy to investigate their possible role in susceptibility to PD. No significant differences were found in genotype and allele frequencies between PD and controls for all the polymorphisms studied, suggesting that these variants do not contribute significantly to the risk of PD.
Asunto(s)
Estudios de Asociación Genética/métodos , Antígenos de Histocompatibilidad Clase I/genética , Proteínas de la Membrana/genética , Enfermedad de Parkinson/genética , Polimorfismo Genético/genética , Receptores de Transferrina/genética , Transferrina/genética , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Proteína de la Hemocromatosis , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/metabolismo , Transferrina/metabolismoRESUMEN
The major component of Lewy Bodies (LB), the pathological hallmark of Parkinson's disease (PD) is α-synuclein, most prominently phosphorylated at serine 129. G-protein coupled receptor kinase 5 (GRK5) has been reported to phosphorylate α-synuclein in vitro, enhancing the α-synuclein toxicity to dopaminergic neurons in Drosophila model. Moreover, GRK5 was found in LBs from brain of PD patients. A genetic association study performed in the Japanese population revealed haplotypic association of the GRK5 gene with susceptibility to sporadic PD. We aimed at investigating whether four polymorphisms within the GRK5 gene (rs871196, rs2420616, rs7069375, rs4752293) could represent a risk factor for sporadic PD in Southern Italy. We genotyped 446 patients with PD and 450 controls for these markers and did not find any significant association with the disease at allelic, genotypic and haplotypic level. Our results indicate that the GRK5 gene does not confer risk to sporadic PD in our sample from Southern Italy.
Asunto(s)
Quinasa 5 del Receptor Acoplado a Proteína-G/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Enfermedad de Parkinson/enzimología , Enfermedad de Parkinson/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes/genética , Humanos , Desequilibrio de Ligamiento/genética , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Myocardial (123)Metaiodobenzylguanidine (MIBG) enables the assessment of postganglionic sympathetic cardiac innervation. MIBG uptake is decreased in nearly all patients with Parkinson's disease (PD). Our objective was to evaluate MIBG uptake in patients with genetic PD. We investigated MIBG uptake in 14 patients with PD associated with mutations in different genes (Parkin, DJ-1, PINK1, and leucine-rich repeat kinase 2 -LRRK2), in 15 patients with idiopathic PD, and 10 control subjects. The myocardial MIGB uptake was preserved in 3 of the 4 Parkin-associated Parkinsonisms, in 1 of the 2 patients with DJ-1 mutations, in 1 of the 2 brothers with PINK1 mutations, in 3 of the 6 unrelated patients with Gly2019Ser mutation in the LRRK2 gene, whereas it was impaired in all patients with idiopathic PD. MIBG was preserved in all control subjects. Our study shows that myocardial MIGB uptake was normal in 8 of 14 patients with genetic PD, suggesting that cardiac sympathetic denervation occurs less frequently in genetic PD than in idiopathic PD. Our findings also demonstrate that MIGB uptake has a heterogeneous pattern in genetic PD, because it was differently impaired in patients with different mutations in the same gene or with the same gene mutation.
Asunto(s)
3-Yodobencilguanidina/farmacocinética , Miocardio/metabolismo , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/genética , Trastornos Parkinsonianos/diagnóstico , Trastornos Parkinsonianos/genética , Mutación Puntual/genética , Radiofármacos/farmacocinética , Adulto , Análisis Mutacional de ADN , Diagnóstico Diferencial , Femenino , Respuesta Galvánica de la Piel/fisiología , Genotipo , Humanos , Péptidos y Proteínas de Señalización Intracelular/sangre , Péptidos y Proteínas de Señalización Intracelular/genética , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Masculino , Persona de Mediana Edad , Trastornos del Movimiento/diagnóstico , Trastornos del Movimiento/epidemiología , Proteínas Oncogénicas/sangre , Proteínas Oncogénicas/genética , Enfermedad de Parkinson/epidemiología , Trastornos Parkinsonianos/epidemiología , Regiones Promotoras Genéticas , Proteína Desglicasa DJ-1 , Proteínas Quinasas/sangre , Proteínas Quinasas/genética , Proteínas Serina-Treonina Quinasas/sangre , Proteínas Serina-Treonina Quinasas/genética , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Tomografía Computarizada de Emisión de Fotón Único/métodos , Ubiquitina-Proteína Ligasas/sangre , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
We report a family with 5 affected individuals manifesting either essential tremor (ET), Parkinsonism, or both, consistent with pseudo-dominant inheritance of PARK2. Two homozygotes presented postural and kinetic tremor several years before the onset of Parkinsonism. Postural and kinetic tremor mimicking ET was the only feature in 1 homozygous and 2 heterozygous carriers of the mutation. Striatal dopamine transporter density was reduced in accordance with phenotype and number of mutated alleles. In 3 homozygotes and 1 heterozygote, a 2-year follow-up single photon emission computed tomography suggested no progression of nigrostriatal deficit.