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Published in: BMC Psychiatry 1/2021

Open Access 01-12-2021 | Schizophrenia | Research article

Working memory deficits in schizophrenia are associated with the rs34884856 variant and expression levels of the NR4A2 gene in a sample Mexican population: a case control study

Authors: Elizabeth Ruiz-Sánchez, Janet Jiménez-Genchi, Yessica M. Alcántara-Flores, Carlos J. Castañeda-González, Carlos L. Aviña-Cervantes, Petra Yescas, María del Socorro González-Valadez, Nancy Martínez-Rodríguez, Antonio Ríos-Ortiz, Martha González-González, María E. López-Navarro, Patricia Rojas

Published in: BMC Psychiatry | Issue 1/2021

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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.
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Literature
29.
go back to reference Ishiguro H, Okubo Y, Ohtsuki T, Yamakawa-Kobayashi K, Arinami T. Mutation analysis of the retinoid X receptor beta, nuclear-related receptor 1, and peroxisome proliferator-activated receptor alpha genes in schizophrenia and alcohol dependence: possible haplotype association of nuclear-related receptor 1 gene to alcohol dependence. Am J Med Genet. 2002;114(1):15–23. https://doi.org/10.1002/ajmg.1620.CrossRefPubMed Ishiguro H, Okubo Y, Ohtsuki T, Yamakawa-Kobayashi K, Arinami T. Mutation analysis of the retinoid X receptor beta, nuclear-related receptor 1, and peroxisome proliferator-activated receptor alpha genes in schizophrenia and alcohol dependence: possible haplotype association of nuclear-related receptor 1 gene to alcohol dependence. Am J Med Genet. 2002;114(1):15–23. https://​doi.​org/​10.​1002/​ajmg.​1620.CrossRefPubMed
43.
go back to reference American Psychiatric Association. Diagnostic and statistical manual of mental disorders (4th ed., text rev.; DSM-IV-R). Washington, D.C: American Psychiatric Association; 2000. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (4th ed., text rev.; DSM-IV-R). Washington, D.C: American Psychiatric Association; 2000.
45.
go back to reference Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59(Suppl 20):22–33.PubMed Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59(Suppl 20):22–33.PubMed
46.
go back to reference Gamboa R, Hernandez-Pacheco G, Hesiquio R, Zuñiga J, Massó F, Montaño LF, Ramos-Kuri M, Estrada J, Granados J, Vargas-Alarcón G. Apolipoprotein E polymorphism in the Indian and mestizo populations of Mexico. Hum Biol. 2000;72(6):975–81.PubMed Gamboa R, Hernandez-Pacheco G, Hesiquio R, Zuñiga J, Massó F, Montaño LF, Ramos-Kuri M, Estrada J, Granados J, Vargas-Alarcón G. Apolipoprotein E polymorphism in the Indian and mestizo populations of Mexico. Hum Biol. 2000;72(6):975–81.PubMed
47.
go back to reference Sánchez-Serrano C. Mestizaje e historia de la población en México (con un esbozo antropológico de los lacandones de Chiapas). In: Martín MÁ, García BP, editors. Polimorfismo génico (HLA) en poblaciones Hispanoamericanas. Madrid: Real Academia de Ciencias Exactas, Físicas y Naturales; 1996. Sánchez-Serrano C. Mestizaje e historia de la población en México (con un esbozo antropológico de los lacandones de Chiapas). In: Martín MÁ, García BP, editors. Polimorfismo génico (HLA) en poblaciones Hispanoamericanas. Madrid: Real Academia de Ciencias Exactas, Físicas y Naturales; 1996.
48.
go back to reference Tulsky D, Zhu J. Escala Wechsler de Inteligencia para adultos-III. Mexico City: El manual Moderno; 2003. Tulsky D, Zhu J. Escala Wechsler de Inteligencia para adultos-III. Mexico City: El manual Moderno; 2003.
52.
go back to reference Wechsler D. The measurement of adult intelligence. 3rd ed. Baltimore: The Williams & Wilkins Company; 1944. Wechsler D. The measurement of adult intelligence. 3rd ed. Baltimore: The Williams & Wilkins Company; 1944.
53.
go back to reference Wechsler D. WAIS-III WMS-III technical manual. San Antonio: The Psychological Corporation; 2002. Wechsler D. WAIS-III WMS-III technical manual. San Antonio: The Psychological Corporation; 2002.
66.
go back to reference Tirapu-Ustárroz J, Muñoz-Céspedes JM. Memoria y funciones ejecutivas [Memory and the executive functions]. Rev Neurol. 2005;41(8):475–84.PubMed Tirapu-Ustárroz J, Muñoz-Céspedes JM. Memoria y funciones ejecutivas [Memory and the executive functions]. Rev Neurol. 2005;41(8):475–84.PubMed
Metadata
Title
Working memory deficits in schizophrenia are associated with the rs34884856 variant and expression levels of the NR4A2 gene in a sample Mexican population: a case control study
Authors
Elizabeth Ruiz-Sánchez
Janet Jiménez-Genchi
Yessica M. Alcántara-Flores
Carlos J. Castañeda-González
Carlos L. Aviña-Cervantes
Petra Yescas
María del Socorro González-Valadez
Nancy Martínez-Rodríguez
Antonio Ríos-Ortiz
Martha González-González
María E. López-Navarro
Patricia Rojas
Publication date
01-12-2021
Publisher
BioMed Central
Keyword
Schizophrenia
Published in
BMC Psychiatry / Issue 1/2021
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/s12888-021-03081-w

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