HLA-B*40:02 and DRB1*04:03 are risk factors for oxcarbazepine-induced maculopapular eruption.
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.



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.



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.



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.
Department of Neurology, Laboratory for Neurotherapeutics, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.|Program in Neuroscience, Seoul National University College of Medicine, Seoul, Korea.
Jangsup
J
Moon
Department of Neurology, Laboratory for Neurotherapeutics, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.|Program in Neuroscience, Seoul National University College of Medicine, Seoul, Korea.
Tae-Joon
TJ
Kim
Department of Neurology, Laboratory for Neurotherapeutics, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.|Program in Neuroscience, Seoul National University College of Medicine, Seoul, Korea.
Jung-Ah
JA
Lim
Department of Neurology, Soonchunhyang University Seoul Hospital, Seoul, Korea.
Jun-Sang
JS
Sunwoo
Department of Neurology, Kyung Hee University Hospital at Gangdong, Seoul, Korea.
Jung-Ick
JI
Byun
Department of Neurology, Laboratory for Neurotherapeutics, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.|Program in Neuroscience, Seoul National University College of Medicine, Seoul, Korea.
Soon-Tae
ST
Lee
Department of Neurology, Laboratory for Neurotherapeutics, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.|Program in Neuroscience, Seoul National University College of Medicine, Seoul, Korea.
Keun-Hwa
KH
Jung
Department of Neurology, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea.
Kyung-Il
KI
Park
Department of Neurology, Laboratory for Neurotherapeutics, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.|Program in Neuroscience, Seoul National University College of Medicine, Seoul, Korea.
Ki-Young
KY
Jung
Department of Neurology, Laboratory for Neurotherapeutics, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.|Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
Daejong
D
Jeon
Advanced Neural Technologies, Seoul, Korea.
Kyung-Sang
KS
Yu
Advanced Neural Technologies, Seoul, Korea.
In-Jin
IJ
Jang
Department of Neurology, Laboratory for Neurotherapeutics, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.|Program in Neuroscience, Seoul National University College of Medicine, Seoul, Korea.
Kon
K
Chu
Department of Neurology, Laboratory for Neurotherapeutics, Comprehensive Epilepsy Center, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.|Program in Neuroscience, Seoul National University College of Medicine, Seoul, Korea.
Sang Kun
SK
Lee
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics; D002220:Carbamazepine / Q000009:adverse effects / Q000031:analogs & derivatives*; D003875:Drug Eruptions / Q000235:genetics*; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics; D005260:Female; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000078330:Oxcarbazepine; D012307:Risk Factors; D055815:Young Adult
D000927:Anticonvulsants; D015235:HLA-B Antigens; D059811:HLA-DRB1 Chains; C527195:HLA-DRB1*04 antigen; D002220:Carbamazepine; D000078330:Oxcarbazepine
Human leukocyte antigen; Maculopapular eruption; Oxcarbazepine