Allergy Asthma Immunol Res.  2018 Sep;10(5):555-561. 10.4168/aair.2018.10.5.555.

The Fas Signaling Pathway Is a Common Genetic Risk Factor for Severe Cutaneous Drug Adverse Reactions Across Diverse Drugs

• Park HW
• Kim SH
• Chang YS
• Kim SH
• Jee YK
• Lee AY
• Jang IJ
• Park HS
• Min KU

• KMID: 2418052
• DOI: http://doi.org/10.4168/aair.2018.10.5.555

Abstract

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.

Keyword

Drug; Stevens-Johnson syndrome; toxic epidermal necrolysis; genome-wide association study; Fas signaling pathway

MeSH Terms

Cicatrix
Diagnosis
Drug-Related Side Effects and Adverse Reactions
Gene Frequency
Genome-Wide Association Study
Healthy Volunteers
Humans
Korea
Leukocytes
Polymorphism, Single Nucleotide
Risk Factors*
Stevens-Johnson Syndrome

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