FOXP2 expression and gray matter density in the male brains of patients with schizophrenia.
Por:
Sanjuán J, Castro-Martinez X, García-Martí G, González-Fernández J, Sanz-Requena R, Haro JM, Meana JJ, Martí-Bonmatí L, Nacher J, Sebastiá-Ortega N, Gilabert-Juan J and Moltó MD
Publicada:
1 jun 2021
Ahead of Print:
30 jul 2020
Resumen:
Common genetic variants of FOXP2 may contribute to schizophrenia vulnerability, but controversial results have been reported for this proposal. Here we evaluated the potential impact of the common FOXP2 rs2396753 polymorphism in schizophrenia. It was previously reported to be part of a risk haplotype for this disease and to have significant effects on gray matter concentration in the patients. We undertook the first examination into whether rs2396753 affects the brain expression of FOXP2 and a replication study of earlier neuroimaging findings of the influence of this genetic variant on brain structure. FOXP2 expression levels were measured in postmortem prefrontal cortex samples of 84 male subjects (48 patients and 36 controls) from the CIBERSAM Brain and the Stanley Foundation Array Collections. High-resolution anatomical magnetic resonance imaging was performed on 79 male subjects (61 patients, 18 controls) using optimized voxel-based morphometry. We found differences in FOXP2 expression and brain morphometry depending on the rs2396753, relating low FOXP2 mRNA levels with reduction of gray matter density. We detected an interaction between rs2396753 and the clinical groups, showing that heterozygous patients for this polymorphism have gray matter density decrease and low FOXP2 expression comparing with the heterozygous controls. This study shows the importance of independent replication of neuroimaging genetic studies of FOXP2 as a candidate gene in schizophrenia. Furthermore, our results suggest that the FOXP2 rs2396753 affects mRNA levels, thus providing new knowledge about its significance as a potential susceptibility polymorphism in schizophrenia.
Filiaciones:
Sanjuán J:
Spanish National Network for Research in Mental Health CIBERSAM, Valencia, Spain
Unit of Psychiatry, University of Valencia, Valencia, Spain
INCLIVA Biomedical Research Institute, Fundación Investigación Hospital Clínico de Valencia, Valencia, Spain
Castro-Martinez X:
Laboratorio de Genómica de Enfermedades Psiquiátricas y Neurodegenerativas, INMEGEN, Ciudad de México, México
Department of Genetics, University of Valencia, Valencia, Spain
García-Martí G:
Spanish National Network for Research in Mental Health CIBERSAM, Valencia, Spain
Biomedical Engineering Unit / Radiology Department, Quirónsalud Hospital, Valencia, Spain
González-Fernández J:
Department of Genetics, University of Valencia, Valencia, Spain
Sanz-Requena R:
Biomedical Engineering Unit / Radiology Department, Quirónsalud Hospital, Valencia, Spain
Haro JM:
Spanish National Network for Research in Mental Health CIBERSAM, Valencia, Spain
Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, Barcelona, Spain
Meana JJ:
Spanish National Network for Research in Mental Health CIBERSAM, Valencia, Spain
Department of Pharmacology, Universidad del País Vasco/Euskal Herriko Unibertsitatea UPV/EHU, Leioa, Spain
Martí-Bonmatí L:
Biomedical Engineering Unit / Radiology Department, Quirónsalud Hospital, Valencia, Spain
Nacher J:
Spanish National Network for Research in Mental Health CIBERSAM, Valencia, Spain
INCLIVA Biomedical Research Institute, Fundación Investigación Hospital Clínico de Valencia, Valencia, Spain
Neurobiology Unit, Cell Biology Department, Interdisciplinary Research Structure for Biotechnology and Biomedicine (BIOTECMED), Universitat de València, Valencia, Spain
Sebastiá-Ortega N:
Spanish National Network for Research in Mental Health CIBERSAM, Valencia, Spain
Department of Genetics, University of Valencia, Valencia, Spain
Gilabert-Juan J:
Spanish National Network for Research in Mental Health CIBERSAM, Valencia, Spain.
INCLIVA Biomedical Research Institute, Fundación Investigación Hospital Clínico de Valencia, Valencia, Spain.
Department of Genetics, University of Valencia, Valencia, Spain.
Neurobiology Unit, Cell Biology Department, Interdisciplinary Research Structure for Biotechnology and Biomedicine (BIOTECMED), Universitat de València, Valencia, Spain.
Department of Genetics, Universitat de València, Dr. Moliner 50, 46100, Burjassot, Valencia, Spain.
Green Published, hybrid
|