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

Abstract

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. 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-B ∗ 44:03 (OR, 7.2, p=5.5×10 -6, pc=1.1×10 -4) and HLA-C ∗ 07:01 (OR, 6.1, p=7.1×10 -6, pc=1.1×10 -4) 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-B ∗ 44:03 and HLA-C ∗ 07:01 haplotype compared with only 11 of 159 healthy controls (6.9%) (OR=7.1, p=5.5×10 -6). Conclusions HLA-B ∗ 44:03-HLA-C ∗ 07:01 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.