Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans
Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans
复制标题
DOI：
10.1016/j.eplepsyres.2011.08.010
复制
发表时间：
2011-11-01
影响因子：
2.2
通讯作者：
Chang, Yoon-Seok
中科院分区：
文献类型：
--
作者：
Kim, Sae-Hoon;Lee, Kyung Wha;Chang, Yoon-Seok
背景：尽管美国FDA建议在开始卡马西平治疗前，对大多数亚洲人进行HLA- b *1502等位基因筛查，但HLA与卡马西平过敏在非华裔亚洲人群中的关系尚不清楚。本研究调查了韩国人HLA I类基因型与卡马西平诱导的严重皮肤不良反应（SCAR）之间的关系。方法：24例发生卡马西平诱导的SCAR患者（7例为Stevens-Johnson综合征（SJS）， 17例为药物超敏反应综合征（HSS））， 50例卡马西平耐受对照来自韩国药物遗传不良反应研究网络，485例韩国普通人群数据来自先前发表的研究。采用直接DNA序列分析进行HLA-A、-B、-C基因分型。结果：7例SJS患者中仅有1例B*1502等位基因阳性，但CBZ-SJS患者中B*1511等位基因的频率明显高于cbz -耐受对照组（P = 0.011, P-c =无统计学意义；OR = 18.0(2.3-141.2)）。卡马西平诱导的HSS和SCAR中A*3101的频率显著高于卡马西平耐受对照组(P-c = 0.011, OR = 8.8（2.5 ~ 30.7), P-c = 0.013, OR = 7.3(2.3 ~ 22.5)）。卡马西平- sjs组B*1511频率和卡马西平- hss /SCAR组A*3101频率均显著高于普通人群。结论：HLA-B*1502似乎不是卡马西平诱导的SCAR的有效预测指标，而HLA-B*1511和A*3101分别与卡马西平诱导的SJS和HSS/SCAR相关。(C) 2011 Elsevier B.V.版权所有
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. (C) 2011 Elsevier B.V. All rights reserved.