RESUMO
Aim: We investigated GRIN1, GRIN2A, GRIN2B and LINE-1 DNA methylation in first-episode schizophrenia patients, their nonaffected siblings and age- and sex-matched controls testing for associations between DNA methylation and exposition to childhood trauma. Materials & methods: The Childhood Trauma Questionnaire evaluated the history of childhood trauma. Genomic DNA was bisulfite converted and pyrosequencing was employed to quantify DNA methylation. Results:GRIN2A, GRIN2B and LINE-1 DNA methylation was not associated with childhood trauma in patients, siblings and controls. Siblings with childhood trauma had hypermethylation at CpG1 of GRIN1 compared with siblings without trauma. Conclusion: Childhood trauma may influence GRIN1 methylation in subjects with liability to psychosis, but not in frank schizophrenia or controls.
Lay abstract Schizophrenia results from a combination of genetic and environmental influences. We investigated how some changes in genes can be silenced by a process named DNA methylation and may be linked to schizophrenia. For this reason, we hypothesized that childhood trauma, an environmental risk factor, would be associated with DNA methylation in schizophrenia patients compared with their unaffected siblings and controls. Our research has shown that altered blood DNA methylation of one candidate gene for psychiatric disorders may be associated with childhood trauma in the unaffected siblings of schizophrenia patients, but not in frank schizophrenia or controls. We believe that this gene plays an important role in helping identify vulnerable as well as resilient individuals to schizophrenia disorder.
Assuntos
Experiências Adversas da Infância , Suscetibilidade a Doenças , Receptores de N-Metil-D-Aspartato/genética , Esquizofrenia/epidemiologia , Esquizofrenia/etiologia , Adolescente , Adulto , Biomarcadores , Estudos de Casos e Controles , Ilhas de CpG , Metilação de DNA , Feminino , Regulação da Expressão Gênica , Humanos , Elementos Nucleotídeos Longos e Dispersos , Masculino , Pessoa de Meia-Idade , Receptores de N-Metil-D-Aspartato/metabolismo , Medição de Risco , Fatores de Risco , Esquizofrenia/diagnóstico , Irmãos , Adulto JovemRESUMO
El receptor ionotrópico de glutamato activado por N-metil-D-aspartato (iGluR-NMDA) está conformado por tres tipos diferentes de subunidades NR1, NR2A a D y NR3A y B codificadas por los genes GRIN1, GRIN2 y GRIN3. Dado que la variabilidad genómica de los GRIN está estrechamente asociada con la historia genética de la población analizada, era necesario realizar un estudio detallado del gen GRIN1 en la población colombiana. Por ello, en este trabajo se identificaron polimorfismos presentes en la región 5-UTR y en el exón 6 del gen GRIN1, en 101 muestras de sangre de cordón umbilical de recién nacidos sanos del Hospital Universitario San Ignacio de Bogotá, y se encontró que el polimorfismo A1970G con una frecuencia del alelo menor de 28,21%, no difiere de las poblaciones de caucásicos y nativos americanos. El polimorfismo G1140A, con una frecuencia del alelo menor de 1,49%, no mostró diferencias estadísticamente significativas con la población de Taiwán. El polimorfismo A1160G sólo mostró una forma alélica...
The ionotropic glutamate receptor activated by Nmethyl-D-aspartate is composed by three different kinds of subunits NR1, NR2A to D and NR3A and B, which are codified by GRIN1, GRIN2 and GRIN3 genes. Since the GRIN genomic variability is closely related to the genetic history of the studied population, it was necessary to develop a detailed study of the frequency of the polymorphisms of the gene GRIN-1 in Colombian population. The main goal of this research was to identify polymorphisms present in 5-UTR region and exon 6 of gene GRIN1, among 101 samples of umbilical cord taken on filter paper of healthy newborns at the University Hospital San Ignacio in Bogota. It was found that polymorphism A1970G with minor allele frequencies of 28.21%, doesn't differ significantly from the frequencies in Caucasian and native American populations. Polymorphism G1140A with minor allele frequencies of 1.49% did not show any significant statistic difference with the Taiwan population. Polymorphism A1160G just showed one allelic form, the A allele...