PMID- 29369497 OWN - NLM STAT- MEDLINE DCOM- 20181011 LR - 20220410 IS - 1742-7843 (Electronic) IS - 1742-7835 (Linking) VI - 123 IP - 1 DP - 2018 Jul TI - Pharmacogenetics of Risperidone-Induced Insulin Resistance in Children and Adolescents with Autism Spectrum Disorder. PG - 42-50 LID - 10.1111/bcpt.12970 [doi] AB - The purpose of this study was to explore the association of genetic polymorphism of genes related to pharmacokinetics or pharmacodynamics with insulin resistance in children and adolescents with autism spectrum disorder (ASD) and treated with risperidone. All 89 subjects underwent measurement of fasting blood glucose and insulin levels, body-weight and height. Genotyping was performed by TaqMan real-time polymerase chain reaction (PCR) (pharmacokinetics genes: cytochrome P450 2D6 (CYP2D6) *4 (rs3892097), *5 (gene deletion), *10 (rs1065852) and *41 (rs28371725), ATP-binding cassette transporter B1 (ABCB1) 2677 G>T/A (rs2032582) and 3435C>T (rs1045642) and pharmacodynamics genes: dopamine receptor D2 (DRD2) Tag-SNP (C>T) (rs4436578), DRD2 Tag1A (C>T) (rs1800497), leptin gene (LEP) -2548G>A (rs7799039), ghrelin gene (GHRL) -604G>A (rs27647) and brain-derived neurotrophic factor (BDNF) 196G>A (rs6265)). Drug levels were analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results revealed that 5 (5.62%) patients presented with hyperglycaemia. Insulin resistance was detected in 15 (16.85%) patients. Insulin resistance was associated with LEP 2548 G>A and BDNF 196 G>A polymorphism (p = 0.051 and p = 0.03). There was no association of pharmacokinetic gene polymorphisms (CYP2D6 and ABCB1) and risperidone levels with insulin resistance. Multiple regression analysis indicated that BDNF 196 G>A polymorphism was significantly associated with insulin resistance (p = 0.025). This finding suggested that BDNF 196 G>A polymorphism may be a genetic marker for predicting insulin resistance before initiating treatment in patients treated with risperidone. Because of the small sample size, further studies are needed to confirm these results. CI - (c) 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). FAU - Sukasem, Chonlaphat AU - Sukasem C AD - Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. AD - Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand. FAU - Vanwong, Natchaya AU - Vanwong N AD - Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. AD - Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand. FAU - Srisawasdi, Pornpen AU - Srisawasdi P AD - Division of Clinical Chemistry, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. FAU - Ngamsamut, Nattawat AU - Ngamsamut N AD - Department of Mental Health Services, Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital, Ministry of Public Health, Samut Prakan, Thailand. FAU - Nuntamool, Nopphadol AU - Nuntamool N AD - Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. AD - Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand. AD - Molecular Medicine, Faculty of Science, Mahidol University, Bangkok, Thailand. FAU - Hongkaew, Yaowaluck AU - Hongkaew Y AD - Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. AD - Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand. FAU - Puangpetch, Apichaya AU - Puangpetch A AD - Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. AD - Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand. FAU - Chamkrachangpada, Bhunnada AU - Chamkrachangpada B AD - Department of Mental Health Services, Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital, Ministry of Public Health, Samut Prakan, Thailand. FAU - Limsila, Penkhae AU - Limsila P AD - Department of Mental Health Services, Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital, Ministry of Public Health, Samut Prakan, Thailand. LA - eng PT - Journal Article DEP - 20180330 PL - England TA - Basic Clin Pharmacol Toxicol JT - Basic & clinical pharmacology & toxicology JID - 101208422 RN - 0 (ABCB1 protein, human) RN - 0 (ATP Binding Cassette Transporter, Subfamily B) RN - 0 (Antipsychotic Agents) RN - 0 (Blood Glucose) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Insulin) RN - 7171WSG8A2 (BDNF protein, human) RN - EC 1.14.14.1 (Cytochrome P-450 CYP2D6) RN - L6UH7ZF8HC (Risperidone) SB - IM MH - ATP Binding Cassette Transporter, Subfamily B/genetics MH - Adolescent MH - Adult MH - Antipsychotic Agents/*adverse effects/pharmacokinetics MH - Autism Spectrum Disorder/*drug therapy/genetics MH - Blood Glucose MH - Brain-Derived Neurotrophic Factor/*genetics MH - Child MH - Child, Preschool MH - Cytochrome P-450 CYP2D6/genetics MH - Female MH - Genotype MH - Humans MH - Hyperglycemia/blood/chemically induced/genetics MH - Insulin/blood MH - Insulin Resistance/*genetics MH - Male MH - Pharmacogenomic Variants/genetics MH - Risperidone/*adverse effects/pharmacokinetics MH - Young Adult EDAT- 2018/01/26 06:00 MHDA- 2018/10/12 06:00 CRDT- 2018/01/26 06:00 PHST- 2017/09/14 00:00 [received] PHST- 2018/01/15 00:00 [accepted] PHST- 2018/01/26 06:00 [pubmed] PHST- 2018/10/12 06:00 [medline] PHST- 2018/01/26 06:00 [entrez] AID - 10.1111/bcpt.12970 [doi] PST - ppublish SO - Basic Clin Pharmacol Toxicol. 2018 Jul;123(1):42-50. doi: 10.1111/bcpt.12970. Epub 2018 Mar 30.