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Medhasi S.,Mahidol University | Pasomsub E.,Mahidol University | Vanwong N.,Mahidol University | Ngamsamut N.,Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital | And 6 more authors.
Neuropsychiatric Disease and Treatment | Year: 2016

Single-nucleotide polymorphisms (SNPs) among drug-metabolizing enzymes and transporters (DMETs) influence the pharmacokinetic profile of drugs and exhibit intra- and interethnic variations in drug response in terms of efficacy and safety profile. The main objec­tive of this study was to assess the frequency of allelic variants of drug absorption, distribution, metabolism, and elimination-related genes in Thai children and adolescents with autism spectrum disorder. Blood samples were drawn from 119 patients, and DNA was extracted. Genotyping was performed using the DMET Plus microarray platform. The allele frequencies of the DMET markers were generated using the DMET Console software. Thereafter, the genetic variations of significant DMET genes were assessed. The frequencies of SNPs across the genes coding for DMETs were determined. After filtering the SNPs, 489 of the 1,931 SNPs passed quality control. Many clinically relevant SNPs, including CYP2C19*2, CYP2D6*10, CYP3A5*3, and SLCO1B1*5, were found to have frequencies similar to those in the Chinese population. These data are important for further research to investigate the interpatient variability in pharmacoki­netics and pharmacodynamics of drugs in clinical practice. © 2016 Medhasi et al.

Puangpetch A.,Somdech Phra Debaratana Medical Center | Suwannarat P.,Somdech Phra Debaratana Medical Center | Chamnanphol M.,Somdech Phra Debaratana Medical Center | Koomdee N.,Somdech Phra Debaratana Medical Center | And 2 more authors.
Disease Markers | Year: 2015

Autism is a severe neurodevelopmental disorder. Many susceptible causative genes have been identified. Most of the previous reports showed the relationship between the Human Leukocyte Antigen (HLA) gene and etiology of autism. In order to identify HLA-B alleles associated with autism in Thai population, we compared the frequency of HLA-B allele in 364 autistic subjects with 952 normal subjects by using a two-stage sequence-specific oligonucleotide probe system (PCR-SSOP) method based on flow-cytometry technology. HLA-B13:02 (P=0.019, OR = 2.229), HLA-B38:02 (P=0.049, OR = 1.628), HLA-B44:03 (P=0.016, OR = 1.645), and HLA-B56:01 (P = 1.78 × 10-4, OR = 4.927) alleles were significantly increased in autistic subjects compared with normal subjects. Moreover, we found that the HLA-B18:02 (P=0.016, OR = 0.375) and HLA-B46:12 (P=0.008, OR = 0.147) alleles were negatively associated with autism when compared to normal controls. Both alleles might have a protective role in disease development. In addition, four HLA-B genotypes of autistic patients had statistically significant relationship with control groups, consisting of HLA-B3905/5801 (P=0.032, OR = 24.697), HLA-B2704/5801 (P=0.022, OR = 6.872), HLA-B3501/4403 (P=0.021, OR = 30.269), and HLA-B1801/4402 (P = 0.017, OR = 13.757). This is the first report on HLA-B associated with Thai autism and may serve as a marker for genetic susceptibility to autism in Thai population. © 2015 Apichaya Puangpetch et al.

Tan-kam T.,Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital | Suthisisang C.,Mahidol University | Pavasuthipaisit C.,Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital | Limsila P.,Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital | And 2 more authors.
Pharmacogenomics and Personalized Medicine | Year: 2013

This case report highlights the importance of pharmacogenetic testing in the treatment of attention deficit hyperactive disorder (ADHD). A 6-year-old boy diagnosed with ADHD was prescribed methylphenidate 5 mg twice daily (7 am and noon) and the family was compliant with administration of this medication. On the first day of treatment, the patient had an adverse reaction, becoming disobedient, more mischievous, erratic, resistant to discipline, would not go to sleep until midnight, and had a poor appetite. The All-In-One PGX (All-In-One Pharmacogenetics for Antipsychotics test for CYP2D6, CYP2C19, and CYP2C9) was performed using microarray-based and real-time polymerase chain reaction techniques. The genotype of our patient was identified to be CYP2D6*2/*10, with isoforms of the enzyme consistent with a predicted cytochrome P450 2D6 intermediate metabolizer phenotype. Consequently, the physician adjusted the methylphenidate dose to 2.5 mg once daily in the morning. At this dosage, the patient had a good response without any further adverse reactions. Pharmacogenetic testing should be included in the management plan for ADHD. In this case, cooperation between the medical team and the patients' relatives was key to successful treatment. © 2013 Tan-kam et al, publisher and licensee Dove Medical Press Ltd.

Vanwong N.,Mahidol University | Vanwong N.,Somdech Phra Debaratana Medical Center | Ngamsamut N.,Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital | Hongkaew Y.,Mahidol University | And 11 more authors.
Drug Metabolism and Pharmacokinetics | Year: 2016

CYP2D6 is involved in the biotransformation of a large number of drugs, including risperidone. This study was designed to detect CYP2D6 polymorphisms with a Luminex assay, including assessment the relationship of CYP2D6 polymorphisms and risperidone plasma concentration in autism spectrum disorder children (ASD) treated with risperidone. All 84 ASD patients included in this study had been receiving risperidone at least for 1 month. The CYP2D6 genotypes were determined by Luminex assay. Plasma concentrations of risperidone and 9-hydroxyrisperidone were measured using LC/MS/MS. Among the 84 patients, there were 46 (55.42%) classified as EM, 33 (39.76%) as IM, and 4(4.82%) as UM. The plasma concentration of risperidone and risperidone/9-hydroxyrisperidone ratio in the patients were significant differences among the CYP2D6 predicted phenotype group (P = 0.001 and P < 0.0001 respectively). Moreover, the plasma concentration of risperidone and risperidone/9-hydroxyrisperidone ratio in the patients with CYP2D6 activity score 0.5 were significantly higher than those with the CYP2D6 activity score 2.0 (P = 0.004 and P = 0.002 respectively). These findings suggested that the determination of the accurate CYP2D6 genotype-predicted phenotype is essential in the clinical setting and individualization of drug therapy. The use of the Luminex assay for detection of CYP2D6 polymorphisms could help us more accurately identify an individual's CYP2D6 phenotype. Copyright © 2016 The Japanese Society for the Study of Xenobiotics.

Sukasem C.,Mahidol University | Sukasem C.,Somdech Phra Debaratana Medical Center | Hongkaew Y.,Mahidol University | Hongkaew Y.,Somdech Phra Debaratana Medical Center | And 10 more authors.
Journal of Clinical Psychopharmacology | Year: 2016

Objective The aim of the study was to identify the impact of pharmacogenetic markers associated with prolactin concentration in risperidone-treated children and adolescents with autism spectrum disorders. Methods One hundred forty-seven children and adolescents with autism, aged 3 to 19 years, received risperidone. The clinical data of patients were recorded from medical records. Prolactin levels were measured by chemiluminescence immunoassay. Three CYP2D6 single nucleotide polymorphisms, CYP2D6∗4 (1846G>A), ∗10 (100C>T), and ∗41 (2988G>A), 1 gene deletion (∗5), and DRD2 Taq1A (rs1800497) polymorphism were genotyped by TaqMan real-time polymerase chain reaction. Results The 3 common allelic frequencies were CYP2D6∗10 (55.10%), ∗1 (32.65%), and ∗5 (6.12%), respectively. Patients were grouped according to their CYP2D6 genotypes. There was no significant correlation between the concentrations of prolactin among the CYP2D6 genotypes. In addition, there were no statistical differences in the prolactin response among the CYP2D6-predicted phenotypes of extensive metabolizer and intermediate metabolizer. The DRD2 genotype frequencies were Taq1A A2A2 (38.77%), A1A2 (41.50%), and A1A1 (19.73%), respectively. There were statistically significant differences in prolactin level of patients among the 3 groups (P = 0.033). The median prolactin level in patients with DRD2 Taq1A A2A2 (17.80 ng/mL) was significantly higher than A1A2 (17.10 ng/mL) and A1A1 (12.70 ng/mL). Conclusions DRD2 Taq1A A2A2 polymorphisms may play a significant role in the hyperprolactinemia- associated with risperidone treatment in children and adolescent with autism spectrum disorder. Many drugs used chronically in psychiatric diseases exert their effects mainly through the dopamine D2 receptor. It is therefore possible that these drugs could alter the expression of any dopamine receptor, thus affecting the pharmacodynamics characteristics and toxicity of drug substrates during pharmacotherapy. © 2016 Wolters Kluwer Health, Inc.

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