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Sukasem C.,Mahidol University | Sukasem C.,Somdech Phra Debaratana Medical Center | Manosuthi W.,Bamrasnaradura Infectious Diseases Institute | Koomdee N.,Mahidol University | And 12 more authors.

Background: Human immunodeficiency virus type 1 (HIV-1) infections with a plasma efavirenz concentration of <1,000 ng/mL appear to have a high risk for the emergence of drug resistance. In the present study, we assessed the influence of the CYP2B6 polymorphism on the plasma efavirenz level. Methods: CYP2B6 T18492C (rs2279345) in 149 HIV-infected Thai adults were genotyped. Plasma efavirenz concentrations 12 h after dosing were measured using a validated high-performance liquid chromatography. The relationship between the plasma efavirenz level and the CYP2B6 T18492C polymorphism were analysed. Results: Among the 149 patients, the frequency of T18492C heterozygous (T/C) and homozygous mutant (C/C) was 38.26 % (n = 57) and 6.04 % (n = 9), respectively. In the entire cohort, the median efavirenz plasma concentration was 2,410 ng/mL [interquartile range (IQR) 1,460-4,120 ng/mL]. The plasma efavirenz concentration for patients with 18492CC (1,200 ng/mL, IQR 1,050-1,990 ng/mL) or 18492TC (1,900 ng/mL, IQR 1,320-2,510 ng/mL) genotypes were significantly lower than those with homozygous wild type (3,380 ng/mL, IQR 2,040-5,660 ng/mL), P-value < 0.001. Conclusions: The CYP2B6 T18492C polymorphism was significantly associated with lower efavirenz concentrations compared to those with homozygous wild type in HIV-1 infections. The genetic polymorphism CYP2B6 T18492C may be useful for the optimised efavirenz dose. Further studies in the clinical setting will need to be conducted before such an approach can be recommended for widespread use. © 2013 Springer-Verlag. Source

Bushyakanist A.,Mahidol University | Puangpetch A.,Mahidol University | Puangpetch A.,Somdech Phra Debaratana Medical Center | Sukasem C.,Mahidol University | And 2 more authors.
Pharmacogenomics and Personalized Medicine

Objectives: The objectives of this study were to describe the use of pharmacogenetics in clinical practice for the treatment of individuals with human immunodeficiency virus (HIV) infection and to determine the treatment outcomes of HIV-infected patients in whom pharmacogenetic testing was performed. Methods: This study involves a retrospective collection of medical records of HIV-infected patients who attended Ramathibodi Hospital during January 2011 to November 2014 and in whom pharmacogenetic testing was performed. We reviewed patients’ characteristics, reasons for pharmacogenomic testing, results of human leukocyte antigen-B* (HLA-B*) 5701, HLA-B*3505, HLA-B*4001, CYP2B6, and antiretroviral drug (ARV) levels, treatment planning after the physicians were informed the results, and outcome after changing the treatment. Results: A total of 103 HIV-infected patients with a median age of 46 (range, 20–85) years were enrolled, and 68.9% of them were male. The reasons for pharmacogenomic testing were having adverse drug reactions besides rash (37.9%), screening before prescribing ARV (36.9%), choice of next ARV (19.4%), and confirmation of the cause of skin rash (5.8%). After the physicians knew the results, they adjusted the treatment plan including changing the regimens, changing the ARV dose for avoiding toxicity, and stopping ARV. Among 45 patients, side effects, such as dizziness from efavirenz or rash from abacavir, were improved in 96.4%. Among 27 patients, abnormal laboratory results, such as renal insufficiency from tenofovir or anemia from zidovudine, were improved and some returned to normal in 59.3%. HIV RNA was undetectable after treatment adjustment in 94.9%. Conclusion: The benefits of pharmacogenetic testing are either guiding the initial drug regimen or individualizing regimen, increasing efficacy, and simultaneously avoiding adverse drug reactions. Use of pharmacogenetic testing in HIV-infected Thai adults should be considered. © 2015, Bushyakanist et al. Source

Sukasem C.,Mahidol University | Sukasem C.,Somdech Phra Debaratana Medical Center | Puangpetch A.,Mahidol University | Puangpetch A.,Somdech Phra Debaratana Medical Center | And 3 more authors.
Asian Pacific Journal of Allergy and Immunology

Drug hypersensitivity reactions affect many patients leading to a variety of clinical manifestations, mainly the cutaneous adverse reactions ranging from milder skin reactions to severe cutaneous adverse reactions (SCARs). Hypersensitivity reactions are unpredictable and are thought to have an underlying genetic etiology, as suggested by case reports. With the scientific knowledge of pharmacogenomics and the evidence based on the genomic testing, it is possible to identify genetic predisposing factors for these serious adverse reactions and personalize drug therapy. The most significant genetic associations have been identified in the major histocompatibility complex (MHC) genes encoded for human leukocyte antigens (HLA) alleles. Drugs associated with hypersensitivity reactions with strong genetic predisposing factors include abacavir, nevirapine, carbamazepine, and allopurinol. In this review, strong genetic associations of drug-induced SCARs are highlighted so as to improve drug safety and help to select optimal drugs for individual patients. Further investigation, however, is essential for the characterization of other genes involved in the hypersensitivity reactions with the use of several genetic strategies and technologies. Source

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

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. Source

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

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. Source

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