PMID- 27666425 OWN - NLM STAT- MEDLINE DCOM- 20170619 LR - 20221207 IS - 1528-1167 (Electronic) IS - 0013-9580 (Linking) VI - 57 IP - 11 DP - 2016 Nov TI - HLA-B*40:02 and DRB1*04:03 are risk factors for oxcarbazepine-induced maculopapular eruption. PG - 1879-1886 LID - 10.1111/epi.13566 [doi] AB - OBJECTIVE: Oxcarbazepine (OXC) is a widely used antiepileptic drug for the treatment of partial seizures that was developed through structural variation of carbamazepine. Although OXC has a lower risk of cutaneous adverse drug reactions (cADRs) than carbamazepine, cADRs ranging from maculopapular eruption (MPE) to the more severe Stevens-Johnson syndrome and toxic epidermal necrolysis still limit the use of OXC in some patients. A few human leukocyte antigen (HLA)-related genetic risk factors for carbamazepine-induced cADRs have been identified. However, the HLA-related genetic risk factors associated with OXC-induced cADRs are unknown. METHODS: A total of 40 patients who experienced OXC-induced MPE and 70 patients who were tolerant to OXC treatment were included in the study. Genomic DNA was extracted from the peripheral blood of these patients, and high-resolution HLA genotyping was performed. RESULTS: The HLA-B*40:02 and HLA-DRB1*04:03 alleles were significantly associated with OXC-induced MPE compared with the OXC-tolerant group (odds ratio [OR] 4.33, p = 0.018 and OR 14.64, p = 0.003, respectively) and the general Korean population (OR 4.04, p = 0.001 and OR 3.11, p = 0.019, respectively). The HLA-B*15:01 genetic frequency was significantly lower in the OXC-MPE group compared to the OXC-tolerant group (OR 0.18, p = 0.016) and the Korean population (OR 0.22, p = 0.030). The allele frequencies of well-known HLA-related risk factors for carbamazepine-induced cADRs (HLA-B*15:02, A*31:01 and B*15:11) were not different among the three groups. SIGNIFICANCE: This study is the first to demonstrate an association of HLA-B*40:02 and HLA-DRB1*04:03 with OXC hypersensitivity using a large cohort of patients with OXC-induced MPE. These findings should be confirmed in future studies in different ethnic groups. CI - Wiley Periodicals, Inc. (c) 2016 International League Against Epilepsy. FAU - Moon, Jangsup AU - Moon J AD - Department of Neurology, Laboratory for Neurotherapeutics, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea. AD - Program in Neuroscience, Seoul National University College of Medicine, Seoul, Korea. FAU - Kim, Tae-Joon AU - Kim TJ AD - Department of Neurology, Laboratory for Neurotherapeutics, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea. AD - Program in Neuroscience, Seoul National University College of Medicine, Seoul, Korea. FAU - Lim, Jung-Ah AU - Lim JA AD - Department of Neurology, Laboratory for Neurotherapeutics, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea. AD - Program in Neuroscience, Seoul National University College of Medicine, Seoul, Korea. FAU - Sunwoo, Jun-Sang AU - Sunwoo JS AD - Department of Neurology, Soonchunhyang University Seoul Hospital, Seoul, Korea. FAU - Byun, Jung-Ick AU - Byun JI AD - Department of Neurology, Kyung Hee University Hospital at Gangdong, Seoul, Korea. FAU - Lee, Soon-Tae AU - Lee ST AD - Department of Neurology, Laboratory for Neurotherapeutics, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea. AD - Program in Neuroscience, Seoul National University College of Medicine, Seoul, Korea. FAU - Jung, Keun-Hwa AU - Jung KH AD - Department of Neurology, Laboratory for Neurotherapeutics, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea. AD - Program in Neuroscience, Seoul National University College of Medicine, Seoul, Korea. FAU - Park, Kyung-Il AU - Park KI AD - Department of Neurology, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea. FAU - Jung, Ki-Young AU - Jung KY AD - Department of Neurology, Laboratory for Neurotherapeutics, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea. AD - Program in Neuroscience, Seoul National University College of Medicine, Seoul, Korea. FAU - Jeon, Daejong AU - Jeon D AD - Department of Neurology, Laboratory for Neurotherapeutics, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea. AD - Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea. FAU - Yu, Kyung-Sang AU - Yu KS AD - Advanced Neural Technologies, Seoul, Korea. FAU - Jang, In-Jin AU - Jang IJ AD - Advanced Neural Technologies, Seoul, Korea. FAU - Chu, Kon AU - Chu K AD - Department of Neurology, Laboratory for Neurotherapeutics, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea. AD - Program in Neuroscience, Seoul National University College of Medicine, Seoul, Korea. FAU - Lee, Sang Kun AU - Lee SK AD - Department of Neurology, Laboratory for Neurotherapeutics, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea. AD - Program in Neuroscience, Seoul National University College of Medicine, Seoul, Korea. LA - eng PT - Journal Article DEP - 20160926 PL - United States TA - Epilepsia JT - Epilepsia JID - 2983306R RN - 0 (Anticonvulsants) RN - 0 (HLA-B Antigens) RN - 0 (HLA-DRB1 Chains) RN - 0 (HLA-DRB1*04 antigen) RN - 33CM23913M (Carbamazepine) RN - VZI5B1W380 (Oxcarbazepine) SB - IM MH - Adolescent MH - Adult MH - Anticonvulsants/*adverse effects MH - Asian People/genetics MH - Carbamazepine/adverse effects/*analogs & derivatives MH - Drug Eruptions/*genetics MH - Epilepsy/drug therapy/genetics MH - Female MH - Genotype MH - HLA-B Antigens/*genetics MH - HLA-DRB1 Chains/*genetics MH - Humans MH - Male MH - Middle Aged MH - Oxcarbazepine MH - Risk Factors MH - Young Adult OTO - NOTNLM OT - Human leukocyte antigen OT - Maculopapular eruption OT - Oxcarbazepine EDAT- 2016/09/27 06:00 MHDA- 2017/06/20 06:00 CRDT- 2016/09/27 06:00 PHST- 2016/08/25 00:00 [accepted] PHST- 2016/09/27 06:00 [pubmed] PHST- 2017/06/20 06:00 [medline] PHST- 2016/09/27 06:00 [entrez] AID - 10.1111/epi.13566 [doi] PST - ppublish SO - Epilepsia. 2016 Nov;57(11):1879-1886. doi: 10.1111/epi.13566. Epub 2016 Sep 26.