Department of Ophthalmology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Department of Ophthalmology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Br J Ophthalmol. 2018 Sep;102(9):1303-1307. doi: 10.1136/bjophthalmol-2017-311823. Epub 2018 Apr 29.
Polymorphisms in human leucocyte antigen (HLA) class I genes have been found to be associated with cold medicine (CM)-related Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with severe ocular complications (SOC). Because ethnic differences in genetic predisposition to SJS/TEN among different populations have been proposed, we focused on Thai patients and investigated the association between HLA class I genotypes and CM-SJS/TEN with SOC.
This multicentre case-control study was conducted between September 2014 and August 2017. Seventy-one Thai patients with SJS/TEN with SOC and 159 healthy Thai controls were enrolled. HLA typing was performed. Genetic relationships were analysed using Fisher's exact test.
Of 71 patients with SJS/TEN with SOC (28 male, 43 female), 49 (69%) had a history of taking cold medications prior to SJS/TEN onset. The mean age of onset was 26.7±17.1 years (range, 2-77 years). HLA-B44:03 (OR, 7.2, p=5.5×10, pc=1.1×10) and HLA-C07:01 (OR, 6.1, p=7.1×10, pc=1.1×10) showed significant positive associations with Thai patients with CM-SJS/TEN with SOC. Additionally, 17 of 49 patients with CM-SJS/TEN with SOC (34.7%) significantly harboured the HLA-B44:03 and HLA-C07:01 haplotype compared with only 11 of 159 healthy controls (6.9%) (OR=7.1, p=5.5×10).
HLA-B44:03-HLA-C07:01 haplotype is a potential risk factor for CM-SJS/TEN with SOC in the Thai population. This study supports that HLA-B*44:03 might be a common marker for CM-SJS/TEN with SOC in Eurasia populations, including European, Indian, Japanese and Thai.
人类白细胞抗原（HLA）I 类基因的多态性已被发现与感冒药（CM）相关的史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死松解症（TEN）伴有严重眼部并发症（SOC）相关。由于不同人群对 SJS/TEN 的遗传易感性存在种族差异，因此我们关注泰国患者，并研究了 HLA I 类基因型与 CM-SJS/TEN 伴 SOC 的相关性。
本研究为多中心病例对照研究，于 2014 年 9 月至 2017 年 8 月进行。纳入 71 例 SJS/TEN 伴 SOC 的泰国患者和 159 例健康泰国对照。进行 HLA 分型。采用 Fisher 确切检验分析遗传关系。
71 例 SJS/TEN 伴 SOC 的患者中（28 例男性，43 例女性），49 例（69%）在 SJS/TEN 发病前有服用感冒药的病史。发病时的平均年龄为 26.7±17.1 岁（范围：2-77 岁）。HLA-B44:03（OR，7.2，p=5.5×10，pc=1.1×10）和 HLA-C07:01（OR，6.1，p=7.1×10，pc=1.1×10）与泰国 CM-SJS/TEN 伴 SOC 患者存在显著正相关。此外，49 例 CM-SJS/TEN 伴 SOC 患者中有 17 例（34.7%）显著携带 HLA-B44:03 和 HLA-C07:01 单体型，而 159 例健康对照者中仅有 11 例（6.9%）（OR=7.1，p=5.5×10）。
HLA-B44:03-HLA-C07:01 单体型是泰国人群 CM-SJS/TEN 伴 SOC 的潜在危险因素。本研究支持 HLA-B*44:03 可能是欧亚人群（包括欧洲、印度、日本和泰国）CM-SJS/TEN 伴 SOC 的共同标志物。
