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

Heung Woo Park1,2, Sang Heon Kim3, Yoon Seok Chang4

  • 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Allergy, Asthma & Immunology Research
|August 9, 2018
PubMed
Abstract

Insights

The Fas signaling pathway may be a common genetic risk factor for severe cutaneous adverse drug reactions (SCARs) across different medications. This study investigated genetic links beyond human leukocyte antigen (HLA) associations.

Area of Science:

  • Pharmacogenomics
  • Immunogenetics
  • Dermatology

Background:

  • Human leukocyte antigen (HLA) is a primary genetic risk factor for severe cutaneous adverse drug reactions (SCARs).
  • Emerging evidence suggests additional genetic factors contribute to SCARs beyond drug-specific HLA associations.

Purpose of the Study:

  • To identify a shared genetic risk factor for SCARs applicable across various drugs.
  • To explore genetic predispositions to SCARs independent of known HLA associations.

Main Methods:

  • Conducted two independent genome-wide association studies (GWASs) involving SCAR patients and healthy controls in Korea.
  • Analyzed top-ranked single nucleotide polymorphisms (SNPs) and performed pathway-level analysis using ConsensusPathDB.

Main Results:

  • No single nucleotide polymorphism (SNP) reached genome-wide significance in either GWAS.
  • Pathway analysis revealed significant over-representation of the Fas signaling pathway in gene sets from both GWASs.

Conclusions:

  • The Fas signaling pathway is implicated as a potential common genetic risk factor for SCARs.
  • Findings suggest a broader genetic basis for SCARs involving pathways beyond HLA.
Keywords:
DrugFas signaling pathwayStevens-Johnson syndromegenome-wide association studytoxic epidermal necrolysis

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