PMID- 30088374 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 2092-7355 (Print) IS - 2092-7363 (Electronic) IS - 2092-7355 (Linking) VI - 10 IP - 5 DP - 2018 Sep TI - The Fas Signaling Pathway Is a Common Genetic Risk Factor for Severe Cutaneous Drug Adverse Reactions Across Diverse Drugs. PG - 555-561 LID - 10.4168/aair.2018.10.5.555 [doi] AB - PURPOSE: Human leukocyte antigen (HLA) has been recognized as the most important genetic risk factor for severe cutaneous adverse drug reactions (SCARs) caused by certain drugs. However, cumulated observations suggest the presence of genetic risk factors for SCARs other than drug-specific HLA. We aimed to identify a common genetic risk factor of SCARs across multiple drugs. METHODS: We performed 2 independent genome-wide association studies (GWASs). A total of 68 and 38 subjects with a diagnosis of SCAR were enrolled in each GWAS. Their allele frequencies were compared to those of healthy subjects in Korea. RESULTS: No single nucleotide polymorphism (SNP) with genome-wide significance was found in either GWAS. We next selected and annotated the 200 top-ranked SNPs from each GWAS. These 2 sets of annotated genes were then entered into the web interface of ConsensusPathDB for a pathway-level analysis. The Fas signaling pathway was significantly over-represented in each gene set from the 2 GWASs. CONCLUSIONS: Our observations suggest that the Fas signaling pathway may be a common genetic risk factor for SCARs across multiple drugs. CI - Copyright (c) 2018 The Korean Academy of Asthma, Allergy and Clinical Immunology . The Korean Academy of Pediatric Allergy and Respiratory Disease. FAU - Park, Heung Woo AU - Park HW AUID- ORCID: 0000-0002-6970-3228 AD - Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. AD - Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea. guinea71@snu.ac.kr. FAU - Kim, Sang Heon AU - Kim SH AD - Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea. FAU - Chang, Yoon Seok AU - Chang YS AD - Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. FAU - Kim, Sang Hoon AU - Kim SH AD - Department of Internal Medicine, Eulji University School of Medicine, Daejeon, Korea. FAU - Jee, Young Koo AU - Jee YK AD - Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea. FAU - Lee, Ai Young AU - Lee AY AD - Department of Dermatology, Dongguk University Ilsan Hospital, Goyang, Korea. FAU - Jang, In Jin AU - Jang IJ AD - Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine, Seoul, Korea. FAU - Park, Hae Sim AU - Park HS AUID- ORCID: 0000-0003-2614-0303 AD - Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea. FAU - Min, Kyung Up AU - Min KU AD - Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. AD - Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea. LA - eng PT - Journal Article PL - Korea (South) TA - Allergy Asthma Immunol Res JT - Allergy, asthma & immunology research JID - 101518382 PMC - PMC6082816 OTO - NOTNLM OT - Drug OT - Fas signaling pathway OT - Stevens-Johnson syndrome OT - genome-wide association study OT - toxic epidermal necrolysis COIS- There are no financial or other issues that might lead to conflict of interest. EDAT- 2018/08/09 06:00 MHDA- 2018/08/09 06:01 PMCR- 2018/09/01 CRDT- 2018/08/09 06:00 PHST- 2018/02/06 00:00 [received] PHST- 2018/05/25 00:00 [revised] PHST- 2018/06/01 00:00 [accepted] PHST- 2018/08/09 06:00 [entrez] PHST- 2018/08/09 06:00 [pubmed] PHST- 2018/08/09 06:01 [medline] PHST- 2018/09/01 00:00 [pmc-release] AID - 10.555 [pii] AID - 10.4168/aair.2018.10.5.555 [doi] PST - ppublish SO - Allergy Asthma Immunol Res. 2018 Sep;10(5):555-561. doi: 10.4168/aair.2018.10.5.555.