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泰国 HLA-B*44:03-HLA-C*07:01 单倍型与感冒药相关的史蒂文斯-约翰逊综合征伴严重眼部并发症的相关性。

Association between HLA-B*44:03-HLA-C*07:01 haplotype and cold medicine-related Stevens-Johnson syndrome with severe ocular complications in Thailand.

机构信息

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.

出版信息

Br J Ophthalmol. 2018 Sep;102(9):1303-1307. doi: 10.1136/bjophthalmol-2017-311823. Epub 2018 Apr 29.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.

摘要

背景

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。

方法

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。

结果

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)。

结论

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。

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