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Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans

2011; Elsevier BV; Volume: 97; Issue: 1-2 Linguagem: Inglês

10.1016/j.eplepsyres.2011.08.010

1872-6844

Sae‐Hoon Kim, Kyung Wha Lee, Woo‐Jung Song, Sang‐Heon Kim, Young‐Koo Jee, Sang Min Lee, Hye–Ryun Kang, Heung‐Woo Park, Sang‐Heon Cho, Seong-Ho Park, Kyung‐Up Min, Yoon‐Seok Chang,

Contact Dermatitis and Allergies

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. 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. 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, Pc = 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 (Pc = 0.011, OR = 8.8(2.5–30.7) and Pc = 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. 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.