Ophthalmology, Ramathibodi Hospital, Bangkok, Thailand.
Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Br J Ophthalmol. 2022 Jun;106(6):884-888. doi: 10.1136/bjophthalmol-2020-317315. Epub 2020 Nov 23.
BACKGROUND/AIMS: To investigate the association of genetic polymorphisms of human leucocyte antigens (HLA) class I and II genes with acetaminophen-related Steven-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) who developed severe ocular complications (SOC) in the Thai population.
A prospective case-control study including 20 unrelated Thai acetaminophen-related SJS/TEN patients with SOC and 60 Thai healthy volunteers, recruited at three university hospitals in Bangkok, Thailand, from September 2014 to August 2019. HLA genes were analysed using PCR amplification followed by hybridisation with sequence-specific oligonucleotide (SSO) probes with bead-based typing kits. The carrier and gene frequencies of individual HLA alleles in patients were compared with those in control volunteers based on dominant assumption using Fisher's exact test.
Among HLA class I polymorphisms, HLA-A33:03, HLA-B44:03 and HLA-C*07:01 were significantly associated with acetaminophen-related SJS/TEN and SOC with high ORs (95% CI, corrected p value; Pc) in carrier frequency of 5.4 (1.8 to 16.3, Pc=0.0274), 9.0 (95% CI 2.7 to 30.4, Pc=0.0034), and 9.3 (2.8 to 30.2, Pc=0.0022), respectively. There were no significant HLA class II associations with the disease after corrected for a total number of alleles tested.
HLA-B44:03 was strongly associated with acetaminophen-related SJS/TEN patients who developed SOC in Thai population. In addition, we also found moderate to strong associations with HLA-A33:03 and HLA-C*07:01 suggesting their potential roles in the pathogenesis of SOC in acetaminophen-related SJS/TEN.
背景/目的：调查人类白细胞抗原（HLA）I 类和 II 类基因的遗传多态性与在泰国人群中发生严重眼部并发症（SOC）的乙酰氨基酚相关性史蒂文斯-约翰逊综合征（SJS）/中毒性表皮坏死松解症（TEN）之间的关联。
这是一项前瞻性病例对照研究，纳入了 2014 年 9 月至 2019 年 8 月在泰国曼谷的三家大学医院招募的 20 例与乙酰氨基酚相关的 SJS/TEN 患者（伴有 SOC）和 60 例泰国健康志愿者。采用聚合酶链反应（PCR）扩增，然后用珠基分型试剂盒中的序列特异性寡核苷酸（SSO）探针进行杂交，分析 HLA 基因。根据 Fisher 精确检验，基于显性假设，比较患者和对照志愿者中个体 HLA 等位基因的携带和基因频率。
在 HLA I 类多态性中，HLA-A33:03、HLA-B44:03 和 HLA-C*07:01 的携带频率与乙酰氨基酚相关性 SJS/TEN 和 SOC 显著相关，OR 值（95%CI，校正 p 值；Pc）分别为 5.4（1.8 至 16.3，Pc=0.0274）、9.0（95%CI 2.7 至 30.4，Pc=0.0034）和 9.3（2.8 至 30.2，Pc=0.0022）。经过对所测试的等位基因总数进行校正后，HLA II 类与疾病无显著关联。
HLA-B44:03 与泰国人群中发生 SOC 的乙酰氨基酚相关性 SJS/TEN 患者强烈相关。此外，我们还发现与 HLA-A33:03 和 HLA-C*07:01 存在中度至强关联，提示它们在乙酰氨基酚相关性 SJS/TEN 中 SOC 的发病机制中具有潜在作用。
