HLA-A*02:06 and PTGER3 polymorphism exert additive effects in cold medicine-related Stevens–Johnson syndrome with severe ocular complications

Mayumi Ueta; Katsushi Tokunaga; Chie Sotozono; Hiromi Sawai; Kyung Chul Yoon; Mee Kum Kim; Kyoung Yul Seo; Choun Ki Joo; Kei Tashiro; Shigeru Kinoshita

doi:10.1038/HGV.2015.23

HLA-A*02:06 and PTGER3 polymorphism exert additive effects in cold medicine-related Stevens–Johnson syndrome with severe ocular complications

Mayumi Ueta, Katsushi Tokunaga, Chie Sotozono, Hiromi Sawai, Kyung Chul Yoon, Mee Kum Kim, Kyoung Yul Seo, Choun Ki Joo, Kei Tashiro, Shigeru Kinoshita

Department of Ophthalmology

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

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}).

Original language	English
Article number	15023
Journal	Human Genome Variation
Volume	2
Issue number	1
DOIs	https://doi.org/10.1038/HGV.2015.23
Publication status	Published - 2015

Bibliographical note

Funding Information:
The authors thank the patients and volunteers who enrolled in our study. The authors also thank Hiromi Nishigaki for processing the blood samples and performing genotyping and Sangchul Yoon, Hyo Seok Lee and Kyu-Yeon Hwang for their assistance in collecting the blood and DNA samples and the clinical information. This work was supported by grants in aid from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government (BioBank Japan Project), by the JSPS Core-to-Core Program, Advanced Research Networks and, in part, by grants in aid for scientific research from the Japanese Ministry of Health, Labor and Welfare and a research grant from the Kyoto Foundation for the Promotion of Medical Science and the Intramural Research Fund of Kyoto Prefectural University of Medicine. The funding agencies had no role in the study design, data collection or analysis, the decision to publish or the manuscript preparation.

Publisher Copyright:
© 2015 The Japan Society of Human Genetics All rights reserved 2.

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Biology
Genetics

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10.1038/HGV.2015.23

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@article{4aef8db91b47438b9c329af0c1649604,

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).",

author = "Mayumi Ueta and Katsushi Tokunaga and Chie Sotozono and Hiromi Sawai and Yoon, {Kyung Chul} and Kim, {Mee Kum} and Seo, {Kyoung Yul} and Joo, {Choun Ki} and Kei Tashiro and Shigeru Kinoshita",

note = "Funding Information: The authors thank the patients and volunteers who enrolled in our study. The authors also thank Hiromi Nishigaki for processing the blood samples and performing genotyping and Sangchul Yoon, Hyo Seok Lee and Kyu-Yeon Hwang for their assistance in collecting the blood and DNA samples and the clinical information. This work was supported by grants in aid from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government (BioBank Japan Project), by the JSPS Core-to-Core Program, Advanced Research Networks and, in part, by grants in aid for scientific research from the Japanese Ministry of Health, Labor and Welfare and a research grant from the Kyoto Foundation for the Promotion of Medical Science and the Intramural Research Fund of Kyoto Prefectural University of Medicine. The funding agencies had no role in the study design, data collection or analysis, the decision to publish or the manuscript preparation. Publisher Copyright: {\textcopyright} 2015 The Japan Society of Human Genetics All rights reserved 2.",

year = "2015",

doi = "10.1038/HGV.2015.23",

language = "English",

volume = "2",

journal = "Human Genome Variation",

issn = "2054-345X",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - HLA-A*02:06 and PTGER3 polymorphism exert additive effects in cold medicine-related Stevens–Johnson syndrome with severe ocular complications

AU - Ueta, Mayumi

AU - Tokunaga, Katsushi

AU - Sotozono, Chie

AU - Sawai, Hiromi

AU - Yoon, Kyung Chul

AU - Kim, Mee Kum

AU - Seo, Kyoung Yul

AU - Joo, Choun Ki

AU - Tashiro, Kei

AU - Kinoshita, Shigeru

N1 - Funding Information: The authors thank the patients and volunteers who enrolled in our study. The authors also thank Hiromi Nishigaki for processing the blood samples and performing genotyping and Sangchul Yoon, Hyo Seok Lee and Kyu-Yeon Hwang for their assistance in collecting the blood and DNA samples and the clinical information. This work was supported by grants in aid from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government (BioBank Japan Project), by the JSPS Core-to-Core Program, Advanced Research Networks and, in part, by grants in aid for scientific research from the Japanese Ministry of Health, Labor and Welfare and a research grant from the Kyoto Foundation for the Promotion of Medical Science and the Intramural Research Fund of Kyoto Prefectural University of Medicine. The funding agencies had no role in the study design, data collection or analysis, the decision to publish or the manuscript preparation. Publisher Copyright: © 2015 The Japan Society of Human Genetics All rights reserved 2.

PY - 2015

Y1 - 2015

N2 - 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).

AB - 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).

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U2 - 10.1038/HGV.2015.23

DO - 10.1038/HGV.2015.23

M3 - Article

AN - SCOPUS:84944106354

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VL - 2

JO - Human Genome Variation

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ER -

HLA-A*02:06 and PTGER3 polymorphism exert additive effects in cold medicine-related Stevens–Johnson syndrome with severe ocular complications

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

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