title: 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.
abstract: 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,ABCB11(c.3084A > G, c.∗420A > G, c.∗368G > A, and c.∗236G > A) andADH7(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,SCLO1B1(c.-11187G > A and c.521T > C),SLCO1B3(c.334G > T, c.699A > G, and c.1557G > A), andSLC7A5c.∗438C > G. Polymorphisms inUGT2B4c.∗448A > G andCYP2D6(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.
authors.affiliation: Department of Pharmacology, Faculty of Science, Mahidol UniversityBangkok, Thailand; Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol UniversityBangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center, Ramathibodi HospitalBangkok, Thailand.
authors.forename: Sadeep
authors.initials: S
authors.lastname: Medhasi
authors.affiliation: Department of Pharmacology, Faculty of Science, Mahidol University Bangkok, Thailand.
authors.forename: Darawan
authors.initials: D
authors.lastname: Pinthong
authors.affiliation: Division of Virology, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University Bangkok, Thailand.
authors.forename: Ekawat
authors.initials: E
authors.lastname: Pasomsub
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol UniversityBangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center, Ramathibodi HospitalBangkok, Thailand.
authors.forename: Natchaya
authors.initials: N
authors.lastname: Vanwong
authors.affiliation: Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital Samut Prakarn, Thailand.
authors.forename: Nattawat
authors.initials: N
authors.lastname: Ngamsamut
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol UniversityBangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center, Ramathibodi HospitalBangkok, Thailand.
authors.forename: Apichaya
authors.initials: A
authors.lastname: Puangpetch
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol UniversityBangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center, Ramathibodi HospitalBangkok, Thailand.
authors.forename: Monpat
authors.initials: M
authors.lastname: Chamnanphon
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol UniversityBangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center, Ramathibodi HospitalBangkok, Thailand.
authors.forename: Yaowaluck
authors.initials: Y
authors.lastname: Hongkaew
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol UniversityBangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center, Ramathibodi HospitalBangkok, Thailand.
authors.forename: Jirawat
authors.initials: J
authors.lastname: Pratoomwun
authors.affiliation: Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital Samut Prakarn, Thailand.
authors.forename: Penkhae
authors.initials: P
authors.lastname: Limsila
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol UniversityBangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center, Ramathibodi HospitalBangkok, Thailand.
authors.forename: Chonlaphat
authors.initials: C
authors.lastname: Sukasem
keywords: autism spectrum disorders; drug metabolizing enzymes; pharmacogenomics; risperidone; transporters