RESUMEN
Several studies have, with conflicting results, investigated the relationship between the Val66Met polymorphism in brain-derived neurotrophic factor (BDNF) and attention deficit hyperactivity disorder (ADHD). We assessed longitudinal, quantitative phenotypes of hyperactivity-impulsivity and inattention in order to determine whether the Val66Met polymorphism is associated with age-specific and/or persistent symptoms of hyperactivity-impulsivity and/or inattention in a community-based cohort of 1236 Swedish individuals for which ADHD symptom data were collected when the participants were aged 8-9, 13-14 and 16-17 yr. The Met allele was associated with symptoms of ADHD at ages 8-9 and 13-14 yr. A multivariate regression analysis revealed that the observed effect of the Met allele on ADHD symptoms reflects an influence on persistent hyperactivity-impulsivity symptoms. The present findings support the hypothesis that BDNF is involved in the pathogenesis of ADHD. The results highlight the importance of distinguishing between hyperactivity-impulsivity and inattention, respectively, and demonstrate the value of using a longitudinal approach in genetic studies of ADHD symptoms.
Asunto(s)
Conducta del Adolescente , Trastorno por Déficit de Atención con Hiperactividad/genética , Factor Neurotrófico Derivado del Encéfalo/genética , Conducta Infantil , Polimorfismo de Nucleótido Simple , Adolescente , Factores de Edad , Atención , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/psicología , Niño , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Conducta Impulsiva/genética , Modelos Logísticos , Estudios Longitudinales , Masculino , Análisis Multivariante , Oportunidad Relativa , Fenotipo , Medición de Riesgo , Factores de Riesgo , Encuestas y Cuestionarios , Suecia , Adulto JovenRESUMEN
The key symptoms of Parkinson's disease (PD) are caused by degeneration of dopamine neurons originating in substantia nigra. Whereas, transcription factor LMX1A is crucial for the differentiation of mesencephalic dopamine neurons, LMX1B appears to be important for both the development and the survival of these cells. The aim of this study was to investigate if genetic variation in LMX1A and LMX1B differs between patients with PD (n = 357) and control subjects (n = 1428) by genotyping 33 single nucleotide polymorphisms (SNPs) in LMX1A and 11 SNPs in LMX1B. Three SNPs in LMX1A and one in LMX1B were associated with PD. After splitting for gender, six SNPs were associated with PD in women and four in men. The significances obtained did not survive correction for multiple testing, and our results should hence be interpreted with caution, but are partly in line with a previous report, and should thus be of sufficient interest to encourage further studies of these genes in PD.
Asunto(s)
Proteínas de Homeodominio/genética , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple , Factores de Transcripción/genética , Anciano , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Proteínas con Homeodominio LIM , Masculino , Reacción en Cadena de la Polimerasa , Factores SexualesRESUMEN
Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is a neuron-specific enzyme that removes ubiquitin from the C-terminal end of substrates and a component of the ubiquitin-proteasome system. A protective effect of a UCH-L1 variant, S18Y, was suggested since the common variant was found to be inversely associated with sporadic Parkinson's disease (PD). We investigated the association of S18Y in our Swedish PD material. The tyrosine variant was significantly inversely associated with PD (P=0.049) and with a low age of onset (50 years) (P=0.017) in the case-control material, supporting the hypothesis of a protective function.
Asunto(s)
Predisposición Genética a la Enfermedad , Mutación , Enfermedad de Parkinson/genética , Serina/genética , Tirosina/genética , Ubiquitina Tiolesterasa/genética , Análisis Mutacional de ADN/métodos , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Enfermedad de Parkinson/epidemiología , Suecia/epidemiologíaRESUMEN
Optic perineuritis (OPN) is a rare inflammatory disorder involving the optic nerve sheath characterized by visual loss. OPN may be isolated and idiopathic or part of an underlying disorder. This case series aimed to help clinicians investigate and manage this disorder. Presentation, clinical findings, and treatment of OPN are discussed. After review of medical records at the ophthalmology clinic at Sahlgrenska University hospital in Gothenburg, Sweden, seven OPN patients (three men and four women) were identified and included in the present case series. These included idiopathic cases and patients with underlying disorders. Age at OPN diagnosis ranged from 26 to 64 years (mean age 55 years, median age 58 years). Five of the patients were treated with corticosteroids. This study suggests that a high-dose course of corticosteroids is important in the treatment of OPN in severely affected patients.
RESUMEN
LMX1A is a transcription factor involved in the development of dopamine (DA)-producing neurons in midbrain. Previous research has shown that allelic variations in three LMX1A single nucleotide polymorphisms (SNPs) were related to risk of Parkinson's disease (PD), suggesting that these SNPs may influence the number of mesencephalic DA neurons. Prompted by the established link between striatal DA functions and working memory (WM) performance, we examined two of these SNPs in relation to the ability to benefit from 4 weeks of WM training. One SNP (rs4657412) was strongly associated with the magnitude of training-related gains in verbal WM. The allele linked to larger gains has previously been suggested to be associated with higher dopaminergic nerve cell density. No differential gains of either SNP were observed for spatial WM, and the genotype groups were also indistinguishable in tests of attention, interference control, episodic memory, perceptual speed, and reasoning for both SNPs. This pattern of data is in agreement with previous findings from our group, suggesting that cognitive effects of DA-related genes may be more easily detected in a training context than for single-assessment performance scores.
Asunto(s)
Proteínas de Homeodominio/genética , Aprendizaje/fisiología , Memoria a Corto Plazo/fisiología , Adulto , Alelos , Química Encefálica/genética , Cognición/fisiología , ADN/genética , Interpretación Estadística de Datos , Dopamina/fisiología , Femenino , Genotipo , Humanos , Proteínas con Homeodominio LIM , Masculino , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple/genética , Desempeño Psicomotor/fisiología , Tiempo de Reacción/fisiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Aprendizaje Seriado/fisiología , Caracteres Sexuales , Test de Stroop , Factores de Transcripción , Aprendizaje Verbal/fisiología , Adulto JovenRESUMEN
The early development of dopaminergic pathways has been attributed importance for the aetiology of schizophrenia. Several transcription factors are involved in the survival and maturation of dopamine neurons, including LMX1A, LMX1B and PITX3. The possibility that polymorphisms in these genes may influence the development and/or the maintenance of dopaminergic neurons prompted us to investigate if five single nucleotide polymorphisms (SNPs) previously linked to Parkinson's disease are associated with this disorder. Preliminary evidence that genetic variation in LMX1A (rs6668493, rs4657411), LMX1B (rs10987386) and PITX3 (rs4919621) may increase the risk of developing schizophrenia is presented.
Asunto(s)
Proteínas de Homeodominio/genética , Polimorfismo de Nucleótido Simple , Esquizofrenia/genética , Factores de Transcripción/genética , Alelos , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Proteínas con Homeodominio LIMRESUMEN
The present study investigates the effect of the brain-derived neurotrophic factor (BDNF) val66met polymorphism on change in olfactory function in a large scale, longitudinal population-based sample (n = 836). The subjects were tested on a 13 item force-choice odor identification test on two test occasions over a 5-year-interval. Sex, education, health-related factors, and semantic ability were controlled for in the statistical analyses. Results showed an interaction effect of age and BDNF val66met on olfactory change, such that the magnitude of olfactory decline in the older age cohort (70-90 years old at baseline) was larger for the val homozygote carriers than for the met carriers. The older met carriers did not display larger age-related decline in olfactory function compared to the younger group. The BDNF val66met polymorphism did not affect the rate of decline in the younger age cohort (45-65 years). The findings are discussed in the light of the proposed roles of BDNF in neural development and maintenance.
RESUMEN
PITX3 is a transcription factor of importance for the differentiation and survival of midbrain dopaminergic neurons, the gene of which is disrupted in a putative mouse model for Parkinson's disease (PD). The A-allele of a HapMap tagging SNP (rs4919621) that was genotyped in a population of 361 PD patients, 69 of which had early onset, and in 333 controls, was significantly more common in PD patients with an early age of onset when compared either to controls (p=0.002) or to PD patients with late onset (p=0.001). In contrast, a previous finding suggesting a SNP (rs3758549) in the putative promoter region of the PITX3 gene to be associated with PD could not be replicated.
Asunto(s)
Química Encefálica/genética , Predisposición Genética a la Enfermedad/genética , Proteínas de Homeodominio/genética , Enfermedad de Parkinson/genética , Polimorfismo Genético/genética , Factores de Transcripción/genética , Edad de Inicio , Supervivencia Celular/genética , Análisis Mutacional de ADN , Dopamina/metabolismo , Femenino , Frecuencia de los Genes , Marcadores Genéticos/genética , Pruebas Genéticas , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Degeneración Nerviosa/genética , Degeneración Nerviosa/metabolismo , Neuronas/metabolismo , Enfermedad de Parkinson/metabolismo , Regiones Promotoras Genéticas/genética , Sustancia Negra/metabolismoRESUMEN
Accumulating evidence indicate that cyclooxygenase-2 (COX-2) is of pathophysiological importance for the neurodegeneration in Parkinson's disease (PD). For example, in a large epidemiological study, use of NSAIDs was associated with a lower risk of PD. Genetic variants of the COX-2 gene might therefore influence the risk of developing the disease. The genotype distribution of four common single nucleotide polymorphisms (SNPs) in the COX-2 gene (rs689466:A496G, rs20417:G926C, rs5277:G3050C, rs5275:C8473T) was analyzed in PD patients and control subjects in a Swedish population. No differences could be seen between the PD-patient and controls regarding the A496G, G926C, and G3050C SNPs, but the allele frequency of the C8473T SNP was found to differ when male patients were compared to controls (P = 0.007). In females no difference could be seen between PD-patients and controls. In conclusion, the results suggest a possible influence of the COX-2 C8473T SNP in PD, although it only seems to be of importance in men.