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Title: Associations between HLA class i and cytochrome P450 2C9 genetic polymorphisms and phenytoin-related severe cutaneous adverse reactions in a Thai population
Authors: Wichittra Tassaneeyakul
Napat Prabmeechai
Chonlaphat Sukasem
Thachanan Kongpan
Parinya Konyoung
Pansu Chumworathayi
Somsak Tiamkao
Usanee Khunarkornsiri
Kongkiat Kulkantrakorn
Niwat Saksit
Nontaya Nakkam
Patompong Satapornpong
Suda Vannaprasaht
Alisara Sangviroon
Surakameth Mahasirimongkol
Nuanjun Wichukchinda
Ticha Rerkpattanapipat
Wongwiwat Tassaneeyakul
Khon Kaen University
Faculty of Medicine
Integrated Epilepsy Research Group
Division of Pharmacogenomics and Personalized Medicine
Somdech Phra Debaratana Medical Center (SDMC)
Mahidol University
Police General Hospital
Udonthani Hospital
Faculty of Medicine, Thammasat University
Thailand Ministry of Public Health
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Jan-2016
Citation: Pharmacogenetics and Genomics. Vol.26, No.5 (2016), 225-234
Abstract: © 2016 Wolters Kluwer Health, Inc. All rights reserved. Background Phenytoin is one of the most common causative drugs of several types of severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reactions with eosinophilia and systemic symptoms (DRESS). Genetic polymorphisms of the human leukocyte antigens (HLA) and cytochromes P450 (CYP) have been proposed as key elements for the susceptibility to phenytoin-related SCAR in certain ethnicities. This study investigated the associations between the genetic polymorphisms of HLA class I and CYP2C9 and phenytoin-related SCAR in a Thai population. Materials and methods Sixty phenytoin-related SCAR (i.e. 39 SJS/TEN and 21 DRESS) and 92 phenytoin-tolerant patients were enrolled in the study. The genotypes of HLA class I and CYP2C9 were determined. Results Six HLA alleles including HLA-A∗33:03, HLAB∗c 38:02, HLA-B∗51:01, HLA-B∗56:02, HLA-B∗c58:01, and HLA-C∗14:02 were significantly associated with phenytoinrelated SJS/TEN, whereas only the HLA-B∗51:01 was significantly associated with phenytoin-related DRESS. The odds ratios of phenytoin-related SJS/TEN in the patients who carried one of these alleles ranged from 4-to 10-fold. The frequencies of patients who carried the HLA-B∗15:02 in the SJS/TEN (12.82%) or the DRESS (9.52%) groups were not significantly different from that of the controls (14.13%). The higher risk of phenytoin-related SJS/TEN was observed in the patients with CYP2C9∗3 (odds ratio=4.30, 95% confidence interval=1.41-13.09, P<0.05). Conclusion Neither SJS/TEN nor DRESS caused by phenytoin was significantly associated with the HLAB∗ 15:02. The CYP2C9∗3 variant was significantly associated with phenytoin-related SJS/TEN, but not DRESS. Certain alleles of HLA, particularly HLA-B∗56:02, were significantly associated with phenytoin-related SCAR in the study population.
ISSN: 17446880
Appears in Collections:Scopus 2016-2017

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