Pharmacogenetics of Risperidone and Cardiovascular Risk in Children and Adolescents

Abstract

Objective. To identify the frequency of obesity and metabolic complications in child and adolescent users of risperidone. Potential associations with clinical parameters and SNPs of the HTR2C, DRD2, LEP, LEPR, MC4R, and CYP2D6 genes were analyzed. Methods. Samples from 120 risperidone users (8–20 years old) were collected and SNPs were analyzed, alongside assessment of chronological and bone ages, prescribed and weight-adjusted doses, use of other psychotropic drugs, waist circumference, BMI z-scores, blood pressure, HOMA-IR index, fasting levels of serum glucose, insulin, cholesterol, triglycerides, transaminases, and leptin. Results. Thirty-two (26.7%) patients were overweight and 5 (4.2%) obese. Hypertension was recorded in 8 patients (6.7%), metabolic syndrome in 6 (5%), and increased waist circumference in 20 (16.7%). The HOMA-IR was high for 22 patients (18.3%), while total cholesterol and triglycerides were high in 20 (16.7%) and 41 (34.2%) patients, respectively. SNP associations were found for LEP, HTR2C, and CYP2D6 with BMI; CYP2D6 with blood pressure, ALT, and HOMA-IR; HTR2C and LEPR with leptin levels; MC4R and DRD2 with HOMA-IR; HTR2C with WC; and LEP with ALT. Conclusions. Although not higher than in the general pediatric population, a high frequency of patients was overweight/obese, with abnormalities in metabolic parameters and some pharmacogenetic associations.

Pharmacogenetics of Risperidone‐Induced Insulin Resistance in Children and Adolescents with Autism Spectrum Disorder

“…Secondly, we examined the International HapMap Project database for minor allele frequency more than 0.05 in the Chinese Han in Beijing. Thirdly, significant association has been reported in previous studies; CYP2D6 , ABCB1 , DRD2 , LEP , GHRL , BDNF . Candidate SNPs were identified from all three sources.…”

“…Considering the association between CYP2D6 gene polymorphisms and metabolic adverse effects, the study by Santos‐Júnior et al . determined the relationship between CYP2D6*10 (c.100 C>T) and metabolic parameters in children and adolescents treated with risperidone. They reported that homozygosity ( C/C and T/T ) was associated with a higher HOMA‐IR.…”

“…Genetic CYP2D6 status may correspond to a high degree of interindividual variability in clinical outcome and steady‐state plasma concentrations of risperidone and 9‐hydroxyrisperidone . A previous study reported the relationships of CYP2D6*10 (c.100 C>T) and metabolic parameters in children and adolescents treated with risperidone . However, apart from plasma risperidone levels and their access to the brain, efficacy might depend upon the multidrug‐resistant protein gene ( MDR1 or ABCB1 ), which codes for P‐glycoprotein (P‐gp), the transmembrane efflux transporter.…”

Association between serotonin 2C receptor gene (HTR2C) polymorphisms and psychopathological symptoms in children and adolescents

“…This was a descriptive cross-sectional study. The subjects were children and adolescents who had participated in a previous study that quantified the incidence of obesity, hypertension, insulin resistance, metabolic syndrome, and hyperprolactinemia in children and adolescents to whom risperidone was administered to treat mental and behavioral disorders ( 18 – 20 ). The inclusion criteria allowed for children and adolescents between the ages of 8 and 18 who were treated in the outpatient psychiatric unit of the Universidade Estadual de Campinas (UNICAMP) Hospital das Clínicas, São Paulo, Brazil between March 2014 and August 2015.…”

Corrigendum to “Pharmacogenetics of Risperidone and Cardiovascular Risk in Children and Adolescents”

“…In the article titled “Pharmacogenetics of Risperidone and Cardiovascular Risk in Children and Adolescents” [ 1 ], there was an error in the “Laboratory Evaluation” section, where the selected CYP2D6 SNP is written as rs72552269, and should be corrected to “rs1065852.”…”