Elizabeth Ruiz-Sánchez1, Janet Jiménez-Genchi2, Yessica M Alcántara-Flores1, Carlos J Castañeda-González3, Carlos L Aviña-Cervantes4, Petra Yescas5, María Del Socorro González-Valadez6, Nancy Martínez-Rodríguez7, Antonio Ríos-Ortiz2, Martha González-González8, María E López-Navarro1, Patricia Rojas9. 1. Laboratory of Neurotoxicology, Instituto Nacional de Neurología y Neurocirugía, "Manuel Velasco Suárez", SS, Av. Insurgentes Sur No. 3877, Col. La Fama, C.P. 14269, Mexico City, Mexico. 2. Research Unit, Hospital Psiquiátrico Fray Bernardino Álvarez, Mexico City, Mexico. 3. General Direction, Hospital Psiquiátrico Fray Bernardino Álvarez, Mexico City, Mexico. 4. Department of Psychiatry, Instituto Nacional de Neurología y Neurocirugía, "Manuel Velasco Suárez", SS, Av. Insurgentes Sur No. 3877, Col. La Fama, C.P. 14269, Mexico City, Mexico. 5. Department of Genetics, Instituto Nacional de Neurología y Neurocirugía, "Manuel Velasco Suárez", SS, Av. Insurgentes Sur No. 3877, Col. La Fama, C.P. 14269, Mexico City, Mexico. 6. Health Care Division, Hospital Psiquiátrico Fray Bernardino Álvarez, Mexico City, Mexico. 7. Epidemiology, Endocrinology & Nutrition Research Unit, Hospital Infantil de México "Federico Gómez", Mexico City, Mexico. 8. Unit of Cognition and Behavior, Instituto Nacional de Neurología y Neurocirugía, "Manuel Velasco Suárez", SS, Av. Insurgentes Sur No. 3877, Col. La Fama, C.P. 14269, Mexico City, Mexico. 9. Laboratory of Neurotoxicology, Instituto Nacional de Neurología y Neurocirugía, "Manuel Velasco Suárez", SS, Av. Insurgentes Sur No. 3877, Col. La Fama, C.P. 14269, Mexico City, Mexico. prcastane@hotmail.com.
Abstract
BACKGROUND: Cognitive functions represent useful endophenotypes to identify the association between genetic variants and schizophrenia. In this sense, the NR4A2 gene has been implicated in schizophrenia and cognition in different animal models and clinical trials. We hypothesized that the NR4A2 gene is associated with working memory performance in schizophrenia. This study aimed to analyze two variants and the expression levels of the NR4A2 gene with susceptibility to schizophrenia, as well as to evaluate whether possession of NR4A2 variants influence the possible correlation between gene expression and working memory performance in schizophrenia. METHODS: The current study included 187 schizophrenia patients and 227 controls genotyped for two of the most studied NR4A2 genetic variants in neurological and neuropsychiatric diseases. Genotyping was performed using High Resolution Melt and sequencing techniques. In addition, mRNA expression of NR4A2 was performed in peripheral mononuclear cells of 112 patients and 118 controls. A group of these participants, 54 patients and 87 controls, performed the working memory index of the WAIS III test. RESULTS: Both genotypic frequencies of the two variants and expression levels of the NR4A2 gene showed no significant difference when in patients versus controls. However, patients homozygous for the rs34884856 promoter variant showed a positive correlation between expression levels and auditory working memory. CONCLUSIONS: Our finding suggested that changes in expression levels of the NR4A2 gene could be associated with working memory in schizophrenia depending on patients' genotype in a sample from a Mexican population.
BACKGROUND: Cognitive functions represent useful endophenotypes to identify the association between genetic variants and schizophrenia. In this sense, the NR4A2 gene has been implicated in schizophrenia and cognition in different animal models and clinical trials. We hypothesized that the NR4A2 gene is associated with working memory performance in schizophrenia. This study aimed to analyze two variants and the expression levels of the NR4A2 gene with susceptibility to schizophrenia, as well as to evaluate whether possession of NR4A2 variants influence the possible correlation between gene expression and working memory performance in schizophrenia. METHODS: The current study included 187 schizophrenia patients and 227 controls genotyped for two of the most studied NR4A2 genetic variants in neurological and neuropsychiatric diseases. Genotyping was performed using High Resolution Melt and sequencing techniques. In addition, mRNA expression of NR4A2 was performed in peripheral mononuclear cells of 112 patients and 118 controls. A group of these participants, 54 patients and 87 controls, performed the working memory index of the WAIS III test. RESULTS: Both genotypic frequencies of the two variants and expression levels of the NR4A2 gene showed no significant difference when in patients versus controls. However, patients homozygous for the rs34884856 promoter variant showed a positive correlation between expression levels and auditory working memory. CONCLUSIONS: Our finding suggested that changes in expression levels of the NR4A2 gene could be associated with working memory in schizophrenia depending on patients' genotype in a sample from a Mexican population.
Authors: Wanda I Colón-Cesario; Michelle M Martínez-Montemayor; Sohaira Morales; Jahaira Félix; Juan Cruz; Monique Adorno; Lixmar Pereira; Nydia Colón; Carmen S Maldonado-Vlaar; Sandra Peña de Ortiz Journal: Learn Mem Date: 2006 Nov-Dec Impact factor: 2.460
Authors: D V Sheehan; Y Lecrubier; K H Sheehan; P Amorim; J Janavs; E Weiller; T Hergueta; R Baker; G C Dunbar Journal: J Clin Psychiatry Date: 1998 Impact factor: 4.384
Authors: Lucia A Hindorff; Vence L Bonham; Lawrence C Brody; Margaret E C Ginoza; Carolyn M Hutter; Teri A Manolio; Eric D Green Journal: Nat Rev Genet Date: 2017-11-20 Impact factor: 53.242