Associations between HLA class I and cytochrome P450 2C9 genetic polymorphisms and phenytoin-related severe cutaneous adverse reactions in a Thai population
| Autor: | Ticha Rerkpattanapipat, Napat Prabmeechai, Alisara Sangviroon, Thachanan Kongpan, Somsak Tiamkao, Niwat Saksit, Wichittra Tassaneeyakul, Pansu Chumworathayi, Parinya Konyoung, Surakameth Mahasirimongkol, Chonlaphat Sukasem, Nontaya Nakkam, Kongkiat Kulkantrakorn, Nuanjun Wichukchinda, Patompong Satapornpong, Usanee Khunarkornsiri, Suda Vannaprasaht, Wongwiwat Tassaneeyakul |
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| Rok vydání: | 2016 |
| Předmět: |
Phenytoin
Adult Male Adolescent macromolecular substances Human leukocyte antigen 030226 pharmacology & pharmacy Polymorphism Single Nucleotide 03 medical and health sciences Young Adult 0302 clinical medicine Asian People Thai population Genetics Medicine Eosinophilia Humans Genetic Predisposition to Disease Drug reaction General Pharmacology Toxicology and Pharmaceutics Young adult Molecular Biology CYP2C9 Genetics (clinical) Genetic Association Studies Aged Cytochrome P-450 CYP2C9 Aged 80 and over integumentary system business.industry Middle Aged medicine.disease Thailand Toxic epidermal necrolysis stomatognathic diseases HLA-B Antigens Stevens-Johnson Syndrome Immunology Molecular Medicine Female medicine.symptom business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Pharmacogenetics and genomics. 26(5) |
| ISSN: | 1744-6880 |
| Popis: | 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.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.Six HLA alleles including HLA-A*33:03, HLA-B*38:02, HLA-B*51:01, HLA-B*56:02, HLA-B*58:01, and HLA-C*14:02 were significantly associated with phenytoin-related 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, P0.05).Neither SJS/TEN nor DRESS caused by phenytoin was significantly associated with the HLA-B*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. |
| Databáze: | OpenAIRE |
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