NR3C1 and NR3C2 Genes Increase the Risk of Suicide Attempt in Psychiatric Disorder Patients with History of Childhood Trauma

Abstract

Marco Antonio Sanabrais-Jiménez,1 Ayerim Alma Esquivel-López,2 Carlo Esteban Sotelo-Ramírez,1 Alejandro Aguilar-García,1 Bruno Ordoñez-Martínez,1 Joanna Jiménez-Pavón,3 María Victoria Madrigal-Lara,3 Alan Jair Díaz-Vivanco,3 Beatriz Camarena1 1Departamento de Farmacogenética, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Ciudad de Mexico, Mexico; 2Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de Mexico, Mexico; 3Dirección de Servicios Clínicos, Instituto Nacional de Psiquiatría “Ramón de la Fuente Muñiz”, Ciudad de Mexico, MexicoCorrespondence: Beatriz Camarena, Departamento de Farmacogenética, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calz Mexico-Xochimilco 101, Col. San Lorenzo Huipulco, Ciudad de Mexico, 14370, Mexico, Tel [phone], Email [email protected]: Hypothalamic-pituitary-adrenal axis gene variants and childhood trauma (CT) are considered risk factors for suicide attempt (SA). The aim of the present study was analyzed gene x environment (GxE) interaction of NR3C1, NR3C2, and CT, and NR3C1 and NR3C2 gene expression in the development of SA with CT.Participants and Methods: A total of 516 psychiatric Mexican patients from Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz. Among them, 274 had SA at least once and 242 had not SA. Genetic variants of NR3C1 and NR3C2 were genotyped in all the patients, of which were obtained the CT information from medical records. Additionally, the gene expression of NR3C1 and NR3C2 was also analyzed for a subsample of 96 patients, obtaining the TC information from Childhood Trauma Questionnaire (CTQ).Results: The analysis showed a GxE interaction of NR3C1, NR3C2, and CT (OR=2.8, 95% CI [1.9– 3.9], p< 0.0001). Interactions were also observed with neglect (OR=2.1, 95% CI [1.4– 3.1], p< 0.0001), emotional abuse (OR=2.1, 95% CI [1.5– 3], p< 0.0001), and sexual abuse (OR=2.4, 95% CI [1.4– 2.9], p< 0.0001) in the prediction of SA. The analysis of gene expression identified an overexpression of NR3C1 in SA patients with high scores for physical and sexual abuse (p< 0.0001; p< 0.0006, respectively) and emotional neglect (p=0.014). An underexpression was observed of NR3C2, associated with high scores of trauma subtypes (p< 0.0001) except physical neglect. Additionally, we observed an overexpression of NR3C1 gene in patients with SA carriers of A allele of rs6191 (p=0.0015). Also, overexpression of NR3C1 gene in carriers of G allele of rs6198 and underexpression of NR3C2 gene in carriers of G allele of rs5522 (p< 0.0001).Conclusion: Our findings suggest that genetic variants of NR3C1 and NR3C2 differentially affect expression levels, increasing the susceptibility to SA in psychiatric patients with a history of CT.Keywords: NR3C1, NR3C2, childhood trauma, suicide attempt, gene x environment interaction, gene expression

Keywords

• nr3c1
• nr3c2
• childhood trauma
• suicide attempt
• gene x environment interaction
• gene expression.