Farmacogenética en psiquiatría: estudio de variantes alélicas del CYP450 en pacientes chilenos con patología psiquiátrica

Introduction: Psychiatric disorders are one of the most frequent illnesses in the Chilean population and, even though most of these conditions are effectively pharmacologically treatable, there is a percentage of patients who do not respond adequately or have severe adverse effects that require patients to discontinue their treatment. At present, there is no reliable method to predict which drug treatment will be the best for a given patient. The metabolism of psychotropic drugs is mainly mediated by the enzyme complex Cytochrome P450 (CYP450), which includes the isoforms 1A2, 2C9, 2C19, 2D6, 3A4, and 3A5. The genes that code for these enzymes have polymorphic variants that influence enzyme activity. Identification of these CYP450 polymorphisms allows us to classify patients as poor, intermediate, normal, or ultra-rapid metabolizers, facilitating the design of a personalized drug strategy that is predictably effective for the patient. Objective: Genotyping the most relevant allelic variants of CYP450 1A2, 2C9, 2C19, 2D6, 3A4, and 3A5 in Chilean patients consulting for psychiatric disorders. Results: In this observational, descriptive and exploratory study, the genetic variants of 6 CYP450 enzymes were evaluated by RFLP and sequencing in 158 Chilean patients, consulting for psychiatric disorders whose age range was 6-74 years (median of 35 years), being 66 men and 92 women. The allele frequencies obtained shown as wild allele / polymorphic allele were the following: 1A2 (1A / 1F 0.290 / 0.710); 2C9 (1A / 2A 0.880 / 0.120); 2C19 (1A / 2A 0.885 / 0.115); 2D6 * 2 (1/2 0.590 / 0.410); 2D6 * 3 (1/3 0.985 / 0.0015); 2D6 * 4 (1/4 0.910 / 0.090); 3A4 (1A / 1B 0.935 / 0.065); and 3A5 (1A / 3A 0.115 / 0.885). In our study, the genotype frequencies for all the polymorphisms studied in the population were in Hardy-Weinberg equilibrium. Conclusions: The allelic frequencies obtained for the study group are similar to those described by other authors for both the Chilean population and those of other countries in the world and therefore allow adjusting the drugs doses according to international guidelines on personalized medicine. In psychiatry, having a test that allows us to implement a predictably effective therapy for the patient right from the start can make a big difference in clinical practice.