TY - JOUR
AU - Medhasi, Sadeep
AU - Pinthong, Darawan
AU - Pasomsub, Ekawat
AU - Vanwong, Natchaya
AU - Ngamsamut, Nattawat
AU - Puangpetch, Apichaya
AU - Chamnanphon, Monpat
AU - Hongkaew, Yaowaluck
AU - Pratoomwun, Jirawat
AU - Limsila, Penkhae
AU - Sukasem, Chonlaphat
PY - 2016
M3 - Original Research
TI - 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
JO - Frontiers in Pharmacology
UR - https://www.frontiersin.org/articles/10.3389/fphar.2016.00475
VL - 7
SN - 1663-9812
N2 - 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) and ADH7 (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), and SLC7A5 c.∗438C > G. Polymorphisms in UGT2B4 c.∗448A > G and CYP2D6 (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.
ER -