Potential role of regulatory DNA variants in modifying the risk of severe cutaneous reactions induced by aromatic anti-seizure medications

Mullan KA 1 , Anderson A 2 , Shi YW 3 , Ding JH 4 , Ng CC 5 , Chen Z 2 Show all authors , Baum L 4 , Cherny S 4 , Petrovski S 6 , Sham PC 4 , Lim KS 7 , Liao WP 3 , Kwan P 2

Affiliations 

  • 1 Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
  • 2 Department of Neuroscience, Central Clinical School, Alfred Hospital, Monash University, Melbourne, Victoria, Australia
  • 3 Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China
  • 4 Department of Psychiatry, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China
  • 5 Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
  • 6 Epilepsy Research Centre, Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia
  • 7 Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
Epilepsia, 2022 Feb 16.
PMID: 35170024 DOI: 10.1111/epi.17182

Abstract

OBJECTIVE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions. Antiseizure medications (ASMs) with aromatic ring structure, including carbamazepine, are among the most common culprits. Screening for human leukocyte antigen (HLA) allele HLA-B*15:02 is recommended prior to initiating treatment with carbamazepine in Asians, but this allele has low positive predictive value.

METHODS: We performed whole genome sequencing and analyzed 6 199 696 common variants among 113 aromatic ASM-induced SJS/TEN cases and 84 tolerant controls of Han Chinese ethnicity.

RESULTS: In the primary analysis, nine variants reached genome-wide significance (p 

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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