Neuropsychiatric Disease and Treatment (Nov 2018)
Association study between COMT, DRD2, and DRD3 gene variants and antipsychotic treatment response in Mexican patients with schizophrenia
Abstract
Raul Escamilla,1 Beatriz Camarena,2 Ricardo Saracco-Alvarez,1 Ana Fresán,3 Sandra Hernández,2 Alejandro Aguilar-García2 1Schizophrenia Clinic, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz (INPRFM), Mexico City, Mexico; 2Department of Pharmacogenetics, INPRFM, Mexico City, Mexico; 3Division of Clinical Research, INPRFM, Mexico City, Mexico Purpose: The efficacy of schizophrenia treatments using antipsychotics (APs) has long been established, but the benefit obtained by several patients using conventional APs (typical or atypical) has not been enough. Currently, the genetic study of the primary mechanisms of action of the APs has been focused on the dopaminergic pathways. The objective of this study was to determine if the response phenotypes (responder, resistance to treatment, and ultra-resistance to treatment groups) are associated with six single-nucleotide polymorphisms: COMT (Val158Met), DRD2 (A-241G, C376G, C939T, Taq1A), and DRD3 (Ser9Gly).Patients and methods: We classified the patients through a retrospective/prospective methodology to define response phenotypes.Results: COMT/Val158Met and DRD3/Ser9Gly were associated with the responder group (P<0.05). The single-nucleotide polymorphism A-241G of DRD2 gene was related with the resistant-to-treatment group (P<0.001). Finally, Met/Met of COMT and Ser/Gly of DRD3 genes showed a predictive effect associated with the resistant-to-treatment phenotype.Conclusion: Further analyses should be performed to validate these genetic markers as mediators for the response to APs. Keywords: pharmacogenetics, dopamine, resistant to treatment, ultraresistant to treatment
