[Large-scale genotyping in research into autism spectrum disorders and attention deficit hyperactivity disorder]. / Genotipado a gran escala en la investigación del trastorno del espectro autista y el trastorno por deficit de atención con hiperactividad.

INTRODUCTION AND DEVELOPMENT: Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are two neuropsychiatric disorders beginning in childhood that present a high degree of familial aggregation. ASD is characterised by social interaction and communication disorders, whereas patients with ADHD display persistent inattention and/or hyperactive-impulsive behaviour. With the exception of a few cases of autism in which cytogenetic anomalies or mutations have been reported in specific genes, the aetiology of these diseases remains unknown. This is a group of multifactorial diseases with several genes having a lesser effect and there is also an environmental component. Genetic linkage studies have pointed to about 20 chromosomal regions that could well contain genes that grant susceptibility to autism, to ADHD or to both disorders. The challenge to researchers lies in the clinical characterisation, recruitment of patients with ASD and ADHD, gene dosage quantification studies, comparative genomic methylation and hybridisation in order to identify chromosomal rearrangements in patients with autism and severe mental retardation. CONCLUSIONS: Genotyping large SNP-type collections that are potentially functional in genes that are candidates for these disorders, based on pharmacological, biochemical and neuropathological data together with that coming from animal models and linkage studies in a wide collection of samples from patients and controls, will enable us to identify the genetic components of these pathologies and to define their biological foundations.

[Dementia and cognitive impairment pattern: its association with epsilon4 allele of apolipoprotein E gene]. / Demencia y patrón de deterioro cognitivo: asociación con el alelo epsilon4 del gen de la apolipoproteína E.

INTRODUCTION: The APOE epsilon4 allele is a well-established risk factor for Alzheimer's disease. This disease is characterized by a typical progressive cognitive impairment pattern, different from that of other primary dementias such as dementia with Lewy bodies or frontotemporal and vascular dementias, for which there are no conclusive results on the influence of the APOE genotype. OBJECTIVE: Our aim is to study how the APOE genotype associates with different dementia types, and the association of this genotype with mild cognitive impairment and age related cognitive decline, which might be stages in a continuum between normality and dementia. PATIENTS AND METHODS: From a group of 1,022 people we selected 733 patients with different dementia diagnosis and 205 controls. APOE genotype for each participant in the study was determined. RESULTS: As it was already known, the epsilon4 allele is associated to senile Alzheimer's disease (OR= 5.6; 95% CI= 3.6-8.9; p< 0.001) and presenile Alzheimer's disease (OR= 5.4; 95% CI= 2.1-13.8; p< 0.001). It is also associated to mild cognitive impairment (OR= 3.7; 95% CI= 2.3-6.0; p< 0.001) and to age related cognitive decline (OR= 3.0; 95% CI= 1.2-7.3; p< 0.01). Female Alzheimer patients with at least one epsilon4 allele present significantly an earlier age at onset (epsilon4+= 73.4 +/- 5.4; epsilon4- = 76.9 +/- 5.5; p< 0.001). CONCLUSION: The APOE genotype is associated to Alzheimer's disease and to its cognitive impairment pattern. This association has a growing value according to the degree of clinical impairment. The APOE genotype could be used in differential diagnostic of cognitive impairment.

Demencia y patrón de deterioro cognitivo: asociación con el alelo e4 del gen de la apolipoproteína E / Dementia and cognitive impairment pattern: its association with e4 allele of apolipoprotein E gene

Introducción. El alelo e4 de la APOE es un factor de riesgo bien establecido para la enfermedad de Alzheimer (EA). Esta enfermedad se caracteriza por un patrón de deterioro cognitivo (DC)progresivo bastante típico, diferente del de otras demencias, como la demencia con cuerpos de Lewy, la demencia frontotemporal o la demencia vascular, en las que no se han obtenido resultados concluyentes sobre la influencia de este gen. Objetivo. Estudiar la asociación del genotipo APOE con diferentes tipos de demencia, y la asociación de este genotipo con el deterioro cognitivo ligero (DCL) y eldeterioro cognitivo asociado a la edad (DECAE), posibles estadios de un continuo entre la normalidad y la demencia. Pacientes y métodos. Se reclutaron 1.022 personas, de las que se seleccionaron 733 pacientes con distintos subtipos de demencia y 205 controles, a los que se determinó el genotipo del APOE. Resultados. Como ya se conocía, el alelo e4 se asocia a la EA de edad de inicio senil (OR = 5,6; IC 95 por ciento = 3,6-8,9; p < 0,001) y presenil (OR = 5,4; IC 95 por ciento = 2,1-13,8; p < 0,001). También se asocia al DCL (OR = 3,7; IC 95 por ciento = 2,3-6,0; p < 0,001) y al DECAE (OR = 3,0; IC 95 por ciento = 1,2-7,3; p < 0,01). La edadde inicio de la EA es significativamente inferior en las pacientes que poseen al menos un alelo e4 (e4+ = 73,4 ñ 5,4; e4- = 76,9 ñ 5,5; p <0,001). Conclusiones. El genotipo APOE se asocia a la EA y alpatrón de deterioro que la caracteriza. Esta asociación tiene un valor creciente según el grado de deterioro objetivable. El genotipo APOE podría servir en el diagnóstico diferencial del DC (AU)

Introduction. The APOE e4 allele is a well-established risk factor for Alzheimer’s disease. This disease is characterized by a typical progressive cognitive impairment pattern, different from that of other primary dementias such as dementia with Lewy bodies or frontotemporal and vascular dementias, for which there are no conclusive results on the influence of the APOE genotype. Objective. Our aim is to study how the APOE genotype associates with different dementia types, and the asso ciation of this genotype with mild cognitive impairment and age-related cognitive decline, which might be stages in a continuum between normality and dementia. Patients and methods. From a group of 1.022 people we selected 733 patients with different dementia diagnosys and 205 controls. APOE genotype for each participant in the study was determined. Results. As it was already known, the e4 allele is associated to senile Alzheimer’s disease (OR = 5,6; 95% CI = 3,6-8,9; p < 0,001) and presenile Alzheimer’s disease (OR = 5,4; 95% CI = 2,1-13,8; p < 0,001). It is also associated to mild cognitive impairment (OR = 3,7; 95% CI = 2,3-6,0; p < 0,001) and to age-related cognitive decline (OR = 3,0; 95% CI = 1,2-7,3; p < 0,01). Female Alzheimer patients with at least one e4 allele present significantly an earlier age at onset (e4 + = 73,4 ± 5,4; e4 - = 76,9 ± 5,5; p < 0,001). Conclusion. The APOE genotype is associated to Alzheimer’s disease and to its cognitive impairment pattern. This association has a growing value according to the degree of clinical impairment. The APOE genotype could be used in differential diagnostic of cognitive impairment (AU)