Nuevos polimorfismos implicados en esquizofrenia y en el consumo de cannabis asociado

Plaza Cayón, Alejandro (2019). Nuevos polimorfismos implicados en esquizofrenia y en el consumo de cannabis asociado. Proyecto Fin de Carrera / Trabajo Fin de Grado, E.T.S. de Ingeniería Agronómica, Alimentaria y de Biosistemas (UPM), Madrid.

Description

Title: Nuevos polimorfismos implicados en esquizofrenia y en el consumo de cannabis asociado
Author/s:
  • Plaza Cayón, Alejandro
Contributor/s:
  • Fernández García, Carlos Ernesto
  • Giménez Caminero, María Estela
Item Type: Final Project
Degree: Grado en Biotecnología
Date: June 2019
Subjects:
Faculty: E.T.S. de Ingeniería Agronómica, Alimentaria y de Biosistemas (UPM)
Department: Biotecnología - Biología Vegetal
Creative Commons Licenses: Recognition - No derivative works - Non commercial

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Abstract

Schizophrenia is a complex psychiatric disorder characterized by a heterogeneous clinical presentation with psychotic symptoms, such as hallucinations and delusions, cognitive and behavioral dysfunctions. Several pathological changes commonly appear in schizophrenic patients, such as neurotransmitter dysfunctions, reduction in volume of certain cerebral areas, or decreased number of some subpopulations of neurons and dendritic spines; however, the etiopathogenesis of schizophrenia remains unknown. As a highly polygenic disease, multiple genes and signaling networks are responsible for these neurodevelopmental and neurophysiological alterations. Both common and rare variants in several of these genes have been associated with a higher risk of developing schizophrenia, as have been many environmental factors, such as cannabis exposure. In this study, the objective was to assess the influence of genetic variants (mainly single nucleotide polymorphisms), on the onset of schizophrenia, as well as possible differences in age at onset. Additionally, the influence of cannabis consumption on the development of schizophrenia and its interaction with these genetic variants was studied. A sample of 235 healthy controls and 260 schizophrenic patients was selected, and patients were stratified according to their sex and cannabis consumption. After recruitment, blood and subsequent DNA samples were extracted from each of them, for 13 polymorphisms (rs114010343, rs150252760, rs200286951, rs114052547, rs6723897, rs6736601, rs116575379, rs77567800, rs202174524, rs33995463, rs2494732, rs140395700 and rs150785666), located on candidate genes, to be genotyped. Finally, statistical analysis was performed to reveal potential associations. Despite the low genotype variability in the sample, three polymorphisms (rs6736601, variant of SATB2; rs202174524, variant of C4A, and rs77567800, variant of ARHGEF38) appeared to be associated with the development of schizophrenia, and sex and cannabis use modulate this association. Variant rs6736601 was also associated with cannabis use in schizophrenic women. Differences in age at onset were significant in the polymorphism rs2494732 (AKT1 gene), and were also influenced by cannabis exposure. These 4 associated genes have important roles in cellular signal transduction, gene expression and nervous system’s homeostasis, and mediate key processes in the central nervous system, such as neurogenesis, neuronal migration, development of neurites and shaping of synaptic connections. Additionally, the association of the C4A gene supports the theory of an immune-mediated regulation of neuronal function. Thus, this experiment further evidences that schizophrenia’s pathogenesis involves diverse signaling pathways and processes, in which not only the nervous system, but others (as the immune system) play important roles. More importantly, this work evidences that these alterations are affected by genetic variants, sex, and environmental exposure to cannabis.

More information

Item ID: 57550
DC Identifier: http://oa.upm.es/57550/
OAI Identifier: oai:oa.upm.es:57550
Deposited by: Biblioteca ETSI Agrónomos
Deposited on: 19 Dec 2019 06:29
Last Modified: 19 Dec 2019 06:29
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