The HLA-A*2402/Cw*0102 haplotype is associated with lamotrigine-induced maculopapular eruption in the Korean population.
The use of lamotrigine (LTG) can be limited by the occurrence of cutaneous adverse drug reactions (cADRs) that range from maculopapular eruption (MPE) to the more severe Stevens-Johnson syndrome and toxic epidermal necrolysis. A few human leukocyte antigen (HLA)-related genetic risk factors for carbamazepine-induced cADR have been identified. However, the HLA-related genetic risk factors associated with LTG-induced cADR are not yet well known. We performed HLA genotyping in 50 Korean patients with epilepsy, including 21 patients presenting LTG-induced MPE and 29 LTG-tolerant patients. A significant association between the HLA-A*2402 allele and LTG-induced MPE was identified, in comparison with the LTG-tolerant group (odds ratio [OR] 4.09, p = 0.025) and the general Korean population (OR 3.949, p = 0.005). The frequencies of the Cw*0102 or Cw*0702 alleles were significantly higher in the LTG-MPE group than in the Korean population, whereas the frequency of the A*3303 allele was lower. The coexistence of the A*2402 and Cw*0102 alleles was significantly associated with the LTG-MPE group when compared to the LTG-tolerant group (OR 7.88, p = 0.007). In addition, the Cw*0701 allele was more frequent in the LTG-tolerant group than in the Korean population. These findings suggest the presence of HLA-related genetic risk factors for LTG-induced MPE in the Korean population.
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 Internal Medicine, Institute of Allergy and Clinical Immunology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
Han-Ki
HK
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.
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.
Jun-Sang
JS
Sunwoo
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-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.
Jung-Ah
JA
Lim
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, CHA Bundang Medical Center, CHA University, Seoungnam, Korea.
Jung-Won
JW
Shin
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, 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.|Program in Neuroscience, Seoul National University College of Medicine, Seoul, Korea.
Daejong
D
Jeon
Department of Neurology, Konkuk University College of Medicine, Seoul, Korea.
Dong Wook
DW
Kim
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
Kyung-Sang
KS
Yu
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
In-Jin
IJ
Jang
Department of Internal Medicine, Institute of Allergy and Clinical Immunology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
Hye-Ryun
HR
Kang
Department of Internal Medicine, Institute of Allergy and Clinical Immunology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
Heung-Woo
HW
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.
Sang Kun
SK
Lee
D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects*; D003875:Drug Eruptions / Q000209:etiology* / Q000235:genetics*; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D059871:HLA-A24 Antigen / Q000235:genetics*; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D056910:Republic of Korea; D014227:Triazines / Q000009:adverse effects*; D055815:Young Adult
D000927:Anticonvulsants; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D014227:Triazines; D000077213:Lamotrigine
Cutaneous adverse reaction; HLA; Lamotrigine; Maculopapular eruption; Rash