Association of HLA polymorphisms and acetaminophen-related Steven-Johnson syndrome with severe ocular complications in Thai population
Association of HLA polymorphisms and acetaminophen-related Steven-Johnson syndrome with severe ocular complications in Thai population
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DOI：
10.1136/bjophthalmol-2020-317315
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发表时间：
2022-06-01
影响因子：
4.1
通讯作者：
Kinoshita, Shigeru
中科院分区：
文献类型：
--
作者：
Jongkhajornpong, Passara;Ueta, Mayumi;Kinoshita, Shigeru
背景/目的：研究泰国人群中人类白细胞抗原（HLA）I类和II类基因的遗传多态性与发生严重眼部并发症（SOC）的对乙酰氨基酚相关性Steven-Johnson综合征（SJS）/中毒性表皮坏死松解症（TEN）的相关性。方法一项前瞻性病例对照研究，包括2014年9月至2019年8月在泰国曼谷的三所大学医院招募的20名无亲缘关系的泰国对乙酰氨基酚相关SJS/TEN SOC患者和60名泰国健康志愿者。HLA基因进行了分析，使用PCR扩增，然后杂交与序列特异性寡核苷酸（SSO）探针珠为基础的分型试剂盒。根据显性假设，采用Fisher精确检验比较患者和对照组个体HLA等位基因的携带者和基因频率。结果HLA-A*33：03、HLA-B*44：03和HLA-C*07：01基因多态性与醋氨酚相关的SJS/TEN和SOC显著相关，OR值较高（95% CI，校正p值; Pc），载波频率分别为5.4（1.8 - 16.3，Pc=0.0274）、9.0（95% CI 2.7 - 30.4，Pc=0.0034）和9.3（2.8 - 30.2，Pc=0.0022）。有没有显着的HLA II类与疾病的等位基因总数校正后。结论HLA-B*44：03与泰国人群中发生SOC的对乙酰氨基酚相关SJS/TEN患者密切相关。此外，我们还发现与HLA-A*33：03和HLA-C*07：01存在中度至重度相关性，这表明它们在对乙酰氨基酚相关SJS/TEN的SOC发病机制中可能发挥作用。
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. Methods 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. Results Among HLA class I polymorphisms, HLA-A*33:03, HLA-B*44:03 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. Conclusion HLA-B*44:03 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-A*33:03 and HLA-C*07:01 suggesting their potential roles in the pathogenesis of SOC in acetaminophen-related SJS/TEN.