Pharmacogenomic Study Reveals New Variants of Drug Metabolizing Enzyme and Transporter Genes Associated with Steady-State Plasma Concentrations of Risperidone and 9-Hydroxyrisperidone in Thai Autism Spectrum Disorder Patients

• Published in: Frontiers in pharmacology 2016-12, Vol.7, p.475-475
• Main Authors: Medhasi, Sadeep, Pinthong, Darawan, Pasomsub, Ekawat, Vanwong, Natchaya, Ngamsamut, Nattawat, Puangpetch, Apichaya, Chamnanphon, Monpat, Hongkaew, Yaowaluck, Pratoomwun, Jirawat, Limsila, Penkhae, Sukasem, Chonlaphat
• Format: Article
• Language: English
• Subjects: Autism Spectrum Disorders; drug metabolizing enzymes; pharmacogenomics; Pharmacology; Risperidone; transporters
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2016.00475

The present study sought to investigate the genetic variants in drug metabolizing enzyme and transporter (DMET) genes associated with steady-state plasma concentrations of risperidone among Thai autism spectrum disorder (ASD) patients. ASD patients taking risperidone for at least 1 month were enrolled for this pharmacogenomic study. Genotyping profile was obtained using Affymetrix DMET Plus array interrogating 1931 variants in 231 genes. Steady-state plasma risperidone and 9-hydroxyrisperidone were measured using liquid chromatography/tandem mass spectrometry assay. The final analysis included 483 markers for 167 genes. Six variants, (c.3084A > G, c. 420A > G, c. 368G > A, and c. 236G > A) and (c.690G > A and c.-5360G > A), were found to be associated with plasma concentrations of risperidone. 9-Hydroxyrisperidone and the total active-moiety levels were associated with six gene variants, (c.-11187G > A and c.521T > C), (c.334G > T, c.699A > G, and c.1557G > A), and c. 438C > G. Polymorphisms in c. 448A > G and (c.1661G > C, c.4180G > C, and c.-2178G > A) showed considerable but not significant associations with metabolic ratio. This pharmacogenomic study identifies new genetic variants of DMET genes in monitoring risperidone therapy.