Drug metabolizing enzyme and transporter genes associated with plasma risperidone level in Thai autism spectrum disorder

Abstract

BackgroundThe associations between genetic variants of drug metabolizing enzyme and transporter (DMET) genes and steady-state plasma concentrations of risperidone, 9-hydroxyrisperidone, total active-moiety, and metabolic ratio remain unclear.ObjectiveThe objective of the present study was to present the results of the association between genetic variants of DMET gene and steady-state plasma concentration risperidone and its metabolite using Affymetrix DMET Plus genotyping microarray.MethodsSubjects eligible for this study included male and female adolescents with ASD diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria and being treated with risperidone for at least 4 weeks prior to the blood sample collection. Blood samples were drawn prior to the next dose of risperidone intake to determine the steady-state plasma trough concentrations of risperidone and 9-hydroxyrisperidone. Genotyping profile was obtained using the microarray. Steady-state plasma risperidone and 9-hydroxyrisperidone were measured using liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay.ResultsThe polymorphisms of UGT2B4, CYP2D6 were highly associated with metabolic ratio. Of all the DMET analysis, ABCB11 (3084A > G, 420A > G, 368G > A, and 236G > A) and ADH7 (690G > A and –5360G > A) were found to be associated with plasma concentrations of risperidone (P < 0.01). In addition, 6 genetic variations among the SLC transporter family were associated with the plasma concentration of 9-hydroxyrisperidone.DiscussionsThis study provides a pharmacogenomic approach to investigate further among the DMET genetic variants which influence plasma concentration of risperidone. The treatment of ASD should be based on genetic factors making the challenge of psychopharmacological treatment more efficacious with lesser adverse events.Disclosure of interestThe author has not supplied his/her declaration of competing interest.