title: HLA-A*02:06 and PTGER3 polymorphism exert additive effects in cold medicine-related Stevens-Johnson syndrome with severe ocular complications.
abstract: We previously reported that PTGER3 (prostaglandin E receptor 3 (subtype EP3)) single-nucleotide polymorphisms (SNPs) were associated with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with severe ocular complications (SOC). We also documented that approximately 80% of our SJS/TEN patients had taken cold medicines within several days before disease onset, and we thus designated them cold medicine-related SJS/TEN (CM-SJS/TEN) patients. Moreover, we reported that HLA-A*02:06 with TLR3 polymorphisms exerted more than additive effects in SJS/TEN with SOC. In this study, we focused on CM-SJS/TEN with SOC and analyzed the association with PTGER3 SNPs and an interactive effect between PTGER3 SNPs and HLA-A*02:06 in not only the Japanese but also the Korean population. In the Japanese population, PTGER3 SNP rs1327464 was most significantly associated with CM-SJS/TEN with SOC (G versus A; odds ratio (OR)=0.232, P=7.92×10(-10)), and we found an interaction with additive effects between HLA-A*02:06 and the high-risk genotypes PTGER3 rs1327464 GA or AA (OR=10.8, P=2.56×10(-7)). We also found a significant association between Korean CM-SJS/TEN with SOC and PTGER3 SNP rs1327464 (GG versus GA+AA, OR=0.246, P=0.00101), and we detected an additive effect between HLA-A*02:06 and the high-risk genotypes PTGER3 rs1327464 GA or AA (OR=14.2, P=5.58×10(-6)).
authors.affiliation: Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ueta
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, University of Tokyo , Tokyo, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine , Kyoto, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Sotozono
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, University of Tokyo , Tokyo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sawai
authors.affiliation: Department of Ophthalmology, Chonnam National University , Gwangju, Korea.
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Yoon
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine , Seoul, Korea.
authors.forename: Mee
authors.initials: M
authors.lastname: Kum Kim
authors.affiliation: Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine , Seoul, Korea.
authors.forename: Kyoung
authors.identifier: 0000-0002-9855-1980
authors.initials: K
authors.lastname: Yul Seo
authors.affiliation: Department of Ophthalmology and Visual Science, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea , Seoul, Korea.
authors.forename: Choun-Ki
authors.initials: CK
authors.lastname: Joo
authors.affiliation: Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine , Kyoto, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Tashiro
authors.affiliation: Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine , Kyoto, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kinoshita