AUTHOR=Ueta Mayumi 

TITLE=Susceptibility Genes and HLA for Cold Medicine-Related SJS/TEN with SOC

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.912478

DOI=10.3389/fgene.2022.912478

ISSN=1664-8021

ABSTRACT=<p>We investigated the genetic predisposition for the pathogenesis of Stevens–Johnson syndrome/epidermal necrolysis with severe ocular complications (SJS/TEN with SOC). Cold medicines (CMs) including multi-ingredient cold-medications and non-steroidal anti-inflammatory drugs (NSAIDs) were implicated in the development of SJS/TEN with SOC. Studies on the association between HLA genotypes and CM-related SJS/TEN with SOC (CM-SJS/TEN with SOC) revealed an association with <italic>HLA-A*02:06</italic> in the Japanese; it may be a marker in Koreans. <italic>HLA-B*44:03</italic> was associated with the Japanese, Thais, and Indians; in Brazilians of European ancestry, it may be a positive marker. <italic>PTGER3</italic> is a susceptibility gene; <italic>HLA-A*02:06</italic> and <italic>PTGER3</italic> polymorphisms exerted additive effects in Japanese and Korean patients. A genome-wide association study showed that <italic>IKZF1</italic> was associated with the Japanese. A meta-analysis including Japanese, Koreans, Indians, and Brazilians also revealed an association between CM-SJS/TEN with SOC and <italic>IKZF1.</italic> The upregulation of hsa-miR-628-3p in the plasma of SJS/TEN with SOC patients may suppress the expression of <italic>TLR3</italic> and innate immune-related genes. Not only CMs but also the interaction of <italic>TLR3</italic>, <italic>PTGER3</italic>, <italic>IKZF1</italic>, and <italic>HLA</italic> and maybe some microbial infections are necessary for the onset of SJS/TEN with SOC.</p>