RESUMEN
BACKGROUND: Oxidative stress is a central factor in the pathogenesis of Parkinson's disease (PD). Heme oxygenase-1 (HO-1) is an antioxidant protein expressed in response to oxidative challenge, and its expression levels are inversely correlated with glycogen synthase kinase-3beta (GSK3beta) activity. Underexpression of HO-1 in concert with an upregulation of GSK3beta would result in a less effective antioxidant response and might increase the risk of PD. METHODS: We examined two functional polymorphism in the promoter regions of HO-1 (-413, rs2071746) and GSK3beta (-157, rs6438552) in a group of 251 Spanish patients with PD and 234 controls. RESULTS: Subjects carrying both the HO-1 (-413, rs2071746) TT genotype and the GSK3beta (-157, rs6438552) TT genotype had a four times higher risk of developing PD than subjects without these genotypes (adjusted by age and sex OR = 4.12; 95% CI = 1.45-11.71; Bonferroni corrected P = 0.024). CONCLUSIONS: Considering synergistic effects between polymorphisms in oxidative stress-related genes may help in determining the risk profile for PD.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Glucógeno Sintasa Quinasa 3/genética , Hemo-Oxigenasa 1/genética , Estrés Oxidativo/genética , Enfermedad de Parkinson/enzimología , Enfermedad de Parkinson/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Frecuencia de los Genes/genética , Genotipo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético/genética , Regiones Promotoras Genéticas/genética , Medición de RiesgoRESUMEN
For the first time, the multilocus approach by the set-association method has been applied for the analysis of a cluster of five genes [tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), IL-8, IL-1alpha and IL-10] involved in the brain neuroinflammatory pathway in Parkinson's disease (PD), in a well-defined group of 197 PD patients and 173 control subjects from Spain. Set-association analysis did not reveal an independent or an interactive effect of these inflammatory genes on the PD risk.
Asunto(s)
Inflamación/genética , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/metabolismo , Femenino , Genotipo , Humanos , Inflamación/complicaciones , Inflamación/metabolismo , Interleucina-10/genética , Interleucina-1alfa/genética , Interleucina-6/genética , Interleucina-8/genética , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , España/epidemiología , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
INTRODUCTION: Listeria monocytogenes is a microorganism with marked tropism towards the central nervous system. One of the commonest forms of presentation is as a meningeal infection. The objective of this study is to describe the epidemiological, clinical and laboratory characteristics and therapeutic implications. PATIENTS AND METHODS: We made a retrospective analysis of four patients, admitted to hospital with the diagnosis of meningeal infection and positive culture for L. monocytogenes in the cerebrospinal fluid (CSF), who were admitted to our centre between 1 January 1996 and 31 December 2000. The overall rate of meningitis due to L. monocytogenes in the province of Segovia is similar to that reported from the USA and Europe (six cases per million inhabitants per year). All the patients were male, aged between 19 and 79 years. The commonest form of presentation was a meningeal syndrome. Analysis of the CSF showed pleocytosis with high protein and low glucose levels. Gram staining was negative in all cases. Initial empirical treatment proved to be correct in two of the four patients. The only predisposing factors observed were alcoholism and diabetes mellitus. All four cases recovered. CONCLUSION: We emphasize the difficulty in diagnosing meningitis due to L. monocytogenes, since the presenting symptoms are relatively non specific, CSF analysis gives variable results and Gram staining is of little use. Clinical suspicion is important so that specific antibiotic treatment may be given to improve the prognosis.
