Pharmacogenomics Factors Influencing the Effect of Risperidone on Prolactin Levels in Thai Pediatric Patients With Autism Spectrum Disorder
We investigated the association between genetic variations in pharmacodynamic genes and risperidone-induced increased prolactin levels in children and adolescents with autism spectrum disorder (ASD). In a retrospective study, variants of pharmacodynamic genes were analyzed in 124 ASD patients treate...
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Frontiers Media S.A.
2021-10-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.743494/full |
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language |
English |
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Article |
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DOAJ |
author |
Yaowaluck Hongkaew Yaowaluck Hongkaew Yaowaluck Hongkaew Andrea Gaedigk Andrea Gaedigk Bob Wilffert Bob Wilffert Roger Gaedigk Roger Gaedigk Wiranpat Kittitharaphan Nattawat Ngamsamut Penkhae Limsila Apichaya Puangpetch Apichaya Puangpetch Rattanaporn Sukprasong Rattanaporn Sukprasong Chonlaphat Sukasem Chonlaphat Sukasem Chonlaphat Sukasem |
spellingShingle |
Yaowaluck Hongkaew Yaowaluck Hongkaew Yaowaluck Hongkaew Andrea Gaedigk Andrea Gaedigk Bob Wilffert Bob Wilffert Roger Gaedigk Roger Gaedigk Wiranpat Kittitharaphan Nattawat Ngamsamut Penkhae Limsila Apichaya Puangpetch Apichaya Puangpetch Rattanaporn Sukprasong Rattanaporn Sukprasong Chonlaphat Sukasem Chonlaphat Sukasem Chonlaphat Sukasem Pharmacogenomics Factors Influencing the Effect of Risperidone on Prolactin Levels in Thai Pediatric Patients With Autism Spectrum Disorder Frontiers in Pharmacology risperidone prolactin autism spectrum disorder genetic risk score dopamine D2 receptor (DRD2) |
author_facet |
Yaowaluck Hongkaew Yaowaluck Hongkaew Yaowaluck Hongkaew Andrea Gaedigk Andrea Gaedigk Bob Wilffert Bob Wilffert Roger Gaedigk Roger Gaedigk Wiranpat Kittitharaphan Nattawat Ngamsamut Penkhae Limsila Apichaya Puangpetch Apichaya Puangpetch Rattanaporn Sukprasong Rattanaporn Sukprasong Chonlaphat Sukasem Chonlaphat Sukasem Chonlaphat Sukasem |
author_sort |
Yaowaluck Hongkaew |
title |
Pharmacogenomics Factors Influencing the Effect of Risperidone on Prolactin Levels in Thai Pediatric Patients With Autism Spectrum Disorder |
title_short |
Pharmacogenomics Factors Influencing the Effect of Risperidone on Prolactin Levels in Thai Pediatric Patients With Autism Spectrum Disorder |
title_full |
Pharmacogenomics Factors Influencing the Effect of Risperidone on Prolactin Levels in Thai Pediatric Patients With Autism Spectrum Disorder |
title_fullStr |
Pharmacogenomics Factors Influencing the Effect of Risperidone on Prolactin Levels in Thai Pediatric Patients With Autism Spectrum Disorder |
title_full_unstemmed |
Pharmacogenomics Factors Influencing the Effect of Risperidone on Prolactin Levels in Thai Pediatric Patients With Autism Spectrum Disorder |
title_sort |
pharmacogenomics factors influencing the effect of risperidone on prolactin levels in thai pediatric patients with autism spectrum disorder |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2021-10-01 |
description |
We investigated the association between genetic variations in pharmacodynamic genes and risperidone-induced increased prolactin levels in children and adolescents with autism spectrum disorder (ASD). In a retrospective study, variants of pharmacodynamic genes were analyzed in 124 ASD patients treated with a risperidone regimen for at least 3 months. To simplify genotype interpretation, we created an algorithm to calculate the dopamine D2 receptor (DRD2) gene genetic risk score. There was no relationship between prolactin levels and single SNPs. However, the H1/H3 diplotype (A2/A2-Cin/Cin-A/G) of DRD2/ankyrin repeat and kinase domain containing 1 (ANKK1) Taq1A, DRD2 -141C indel, and DRD2 -141A>G, which had a genetic risk score of 5.5, was associated with the highest median prolactin levels (23 ng/ml). As the dose-corrected plasma levels of risperidone, 9-OH-risperidone, and the active moiety increased, prolactin levels in patients carrying the H1/H3 diplotype were significantly higher than those of the other diplotypes. DRD2 diplotypes showed significantly high prolactin levels as plasma risperidone levels increased. Lower levels of prolactin were detected in patients who responded to risperidone. This is the first system for describing DRD2 haplotypes using genetic risk scores based on their protein expression. Clinicians should consider using pharmacogenetic-based decision-making in clinical practice to prevent prolactin increase. |
topic |
risperidone prolactin autism spectrum disorder genetic risk score dopamine D2 receptor (DRD2) |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2021.743494/full |
work_keys_str_mv |
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doaj-48831bc95a8741539a1023574ca0a3772021-10-06T11:18:15ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-10-011210.3389/fphar.2021.743494743494Pharmacogenomics Factors Influencing the Effect of Risperidone on Prolactin Levels in Thai Pediatric Patients With Autism Spectrum DisorderYaowaluck Hongkaew0Yaowaluck Hongkaew1Yaowaluck Hongkaew2Andrea Gaedigk3Andrea Gaedigk4Bob Wilffert5Bob Wilffert6Roger Gaedigk7Roger Gaedigk8Wiranpat Kittitharaphan9Nattawat Ngamsamut10Penkhae Limsila11Apichaya Puangpetch12Apichaya Puangpetch13Rattanaporn Sukprasong14Rattanaporn Sukprasong15Chonlaphat Sukasem16Chonlaphat Sukasem17Chonlaphat Sukasem18Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandLaboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, ThailandResearch and Development Laboratory, Bumrungrad International Hospital, Bangkok, ThailandDivision of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Children’s Mercy Kansas City, Kanas City, MO, United StatesSchool of Medicine, University of Missouri-Kansas City, Kansas City, MO, United StatesUnit of PharmacoTherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, NetherlandsDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsDivision of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Children’s Mercy Kansas City, Kanas City, MO, United StatesSchool of Medicine, University of Missouri-Kansas City, Kansas City, MO, United StatesDepartment of Mental Health Services, Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital, Ministry of Public Health, Samut Prakan, ThailandDepartment of Mental Health Services, Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital, Ministry of Public Health, Samut Prakan, ThailandDepartment of Mental Health Services, Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital, Ministry of Public Health, Samut Prakan, ThailandDivision of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandLaboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, ThailandDivision of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandLaboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, ThailandDivision of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandLaboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, ThailandPharmacogenomics and Precision Medicine, Preventive Genomics and Family Check-up Services Center, Bumrungrad International Hospital, Bangkok, ThailandWe investigated the association between genetic variations in pharmacodynamic genes and risperidone-induced increased prolactin levels in children and adolescents with autism spectrum disorder (ASD). In a retrospective study, variants of pharmacodynamic genes were analyzed in 124 ASD patients treated with a risperidone regimen for at least 3 months. To simplify genotype interpretation, we created an algorithm to calculate the dopamine D2 receptor (DRD2) gene genetic risk score. There was no relationship between prolactin levels and single SNPs. However, the H1/H3 diplotype (A2/A2-Cin/Cin-A/G) of DRD2/ankyrin repeat and kinase domain containing 1 (ANKK1) Taq1A, DRD2 -141C indel, and DRD2 -141A>G, which had a genetic risk score of 5.5, was associated with the highest median prolactin levels (23 ng/ml). As the dose-corrected plasma levels of risperidone, 9-OH-risperidone, and the active moiety increased, prolactin levels in patients carrying the H1/H3 diplotype were significantly higher than those of the other diplotypes. DRD2 diplotypes showed significantly high prolactin levels as plasma risperidone levels increased. Lower levels of prolactin were detected in patients who responded to risperidone. This is the first system for describing DRD2 haplotypes using genetic risk scores based on their protein expression. Clinicians should consider using pharmacogenetic-based decision-making in clinical practice to prevent prolactin increase.https://www.frontiersin.org/articles/10.3389/fphar.2021.743494/fullrisperidoneprolactinautism spectrum disordergenetic risk scoredopamine D2 receptor (DRD2) |