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
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 one month were enro...
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doaj-f8285819ebad4aa7b598411d30b5f2142020-11-24T21:33:46ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122016-12-01710.3389/fphar.2016.00475216674Pharmacogenomic 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 patientsSadeep Medhasi0Sadeep Medhasi1Sadeep Medhasi2Darawan Pinthong3Ekawat Pasomsub4Natchaya Vanwong5Natchaya Vanwong6Nattawat Ngamsamut7Apichaya Puangpetch8Apichaya Puangpetch9Monpat Chamnanphon10Monpat Chamnanphon11Yaowaluck Hongkaew12Yaowaluck Hongkaew13Jirawat Pratoomwun14Jirawat Pratoomwun15Penkhae Limsila16Chonlaphat Sukasem17Chonlaphat Sukasem18Mahidol UniversityMahidol UniversitySomdech Phra Debaratana Medical Center,Ramathibodi HospitalMahidol UniversityMahidol UniversityMahidol UniversitySomdech Phra Debaratana Medical Center,Ramathibodi HospitalYuwaprasart Waithayopathum Child and Adolescent Psychiatric HospitalMahidol UniversitySomdech Phra Debaratana Medical Center,Ramathibodi HospitalMahidol UniversitySomdech Phra Debaratana Medical Center,Ramathibodi HospitalMahidol UniversitySomdech Phra Debaratana Medical Center,Ramathibodi HospitalMahidol UniversitySomdech Phra Debaratana Medical Center,Ramathibodi HospitalYuwaprasart Waithayopathum Child and Adolescent Psychiatric HospitalMahidol UniversitySomdech Phra Debaratana Medical Center,Ramathibodi HospitalThe 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 one 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 (LC-MS/MS) 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.http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00475/fullRisperidonepharmacogenomicstransportersAutism Spectrum Disordersdrug metabolizing enzymes |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sadeep Medhasi Sadeep Medhasi Sadeep Medhasi Darawan Pinthong Ekawat Pasomsub Natchaya Vanwong Natchaya Vanwong Nattawat Ngamsamut Apichaya Puangpetch Apichaya Puangpetch Monpat Chamnanphon Monpat Chamnanphon Yaowaluck Hongkaew Yaowaluck Hongkaew Jirawat Pratoomwun Jirawat Pratoomwun Penkhae Limsila Chonlaphat Sukasem Chonlaphat Sukasem |
spellingShingle |
Sadeep Medhasi Sadeep Medhasi Sadeep Medhasi Darawan Pinthong Ekawat Pasomsub Natchaya Vanwong Natchaya Vanwong Nattawat Ngamsamut Apichaya Puangpetch Apichaya Puangpetch Monpat Chamnanphon Monpat Chamnanphon Yaowaluck Hongkaew Yaowaluck Hongkaew Jirawat Pratoomwun Jirawat Pratoomwun Penkhae Limsila Chonlaphat Sukasem Chonlaphat Sukasem 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 Frontiers in Pharmacology Risperidone pharmacogenomics transporters Autism Spectrum Disorders drug metabolizing enzymes |
author_facet |
Sadeep Medhasi Sadeep Medhasi Sadeep Medhasi Darawan Pinthong Ekawat Pasomsub Natchaya Vanwong Natchaya Vanwong Nattawat Ngamsamut Apichaya Puangpetch Apichaya Puangpetch Monpat Chamnanphon Monpat Chamnanphon Yaowaluck Hongkaew Yaowaluck Hongkaew Jirawat Pratoomwun Jirawat Pratoomwun Penkhae Limsila Chonlaphat Sukasem Chonlaphat Sukasem |
author_sort |
Sadeep Medhasi |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2016-12-01 |
description |
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 one 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 (LC-MS/MS) 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. |
topic |
Risperidone pharmacogenomics transporters Autism Spectrum Disorders drug metabolizing enzymes |
url |
http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00475/full |
work_keys_str_mv |
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