title: Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans.
abstract: BACKGROUND
  Although the US FDA recommends screening for HLA-B*1502 allele in most of Asian ancestry before initiating carbamazepine therapy, the HLA associations with carbamazepine hypersensitivity in non-Chinese Asian populations remain unclear. This study investigated the association between the HLA class I genotype and carbamazepine-induced severe cutaneous adverse reaction (SCAR) in Koreans.
  
  
  METHODS
  Twenty-four patients who had developed carbamazepine-induced SCAR (7 Stevens-Johnson syndrome (SJS), 17 drug hypersensitivity syndrome (HSS)), 50 carbamazepine-tolerant controls from the Korean Pharmacogenetic Adverse Drug Reaction Research Network and data of 485 Korean general population from a previously published study were recruited. HLA-A, -B, and -C genotyping was performed by direct DNA sequence analysis.
  
  
  RESULTS
  Only one of the seven SJS patients was positive for the B*1502 allele, but the frequency of B*1511 was much higher in the patients with CBZ-SJS than in the CBZ-tolerant control patients (P=0.011, P(c)=not significant; OR=18.0(2.3-141.2)). The frequencies of A*3101 in carbamazepine-induced HSS and SCAR were significantly higher than those in carbamazepine-tolerant controls (P(c)=0.011, OR=8.8(2.5-30.7) and P(c)=0.013, OR=7.3(2.3-22.5), respectively). The frequencies of B*1511 in carbamazepine-SJS and A*3101 in carbamazepine-HSS/SCAR were significantly higher than those in the general population.
  
  
  CONCLUSIONS
  HLA-B*1502 does not seem to be an effective predictive marker for carbamazepine-induced SCAR, while HLA-B*1511 and A*3101 was associated with carbamazepine-induced SJS and HSS/SCAR respectively in the Korean population.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Republic of Korea.
authors.forename: Sae-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Kyung Wha
authors.initials: KW
authors.lastname: Lee
authors.forename: Woo-Jung
authors.initials: WJ
authors.lastname: Song
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Kim
authors.forename: Young-Koo
authors.initials: YK
authors.lastname: Jee
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Lee
authors.forename: Hye-Ryun
authors.initials: HR
authors.lastname: Kang
authors.forename: Heung-Woo
authors.initials: HW
authors.lastname: Park
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Cho
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Park
authors.forename: Kyung-Up
authors.initials: KU
authors.lastname: Min
authors.forename: Yoon-Seok
authors.initials: YS
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D002220:Carbamazepine / Q000009:adverse effects*; D003875:Drug Eruptions / Q000208:ethnology* / Q000235:genetics*; D004827:Epilepsy / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005838:Genotype; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000706:statistics & numerical data; D011237:Predictive Value of Tests; D056910:Republic of Korea; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced* / Q000208:ethnology / Q000235:genetics*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D015395:Histocompatibility Antigens Class I; D002220:Carbamazepine