Work

Pharmacogenomics predictors of aromatic antiepileptic drugs-induced SCARs in the Iraqi patients

Year: 2024

Type: article

Abstract: Introduction Severe cutaneous adverse reactions (SCARs) are life-threatening and often linked to antiepileptic drugs (AEDs). Common types of SCARs include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). Immune-mediated mechanisms involving human leukocyte antigen ( HLA ) alleles have been implicated in the pathogenesis of this reaction. This study examines the association between specific HLA alleles ( HLA-A, -B , and - DRB1 ) and AED-induced SCARs in the Iraqi population. Methodology A total of 50 patients diagnosed with SCARs and 90 tolerant controls were recruited from Dr. Saad Al-Wattari Hospital for Neurological Sciences and Baghdad Hospital - Medical City. HLA genotyping was performed using PCR-SSO method from peripheral blood samples. Statistical comparisons were made using the t -test or chi-square test, while univariate logistic regression with Bonferroni's correction (p < 0.05) were used to assess associations between HLA alleles and SCARs. Results Among the patients, SJS was the most prevalent type of SCARs observed. Analysis of HLA allele frequencies revealed significant associations between specific alleles. HLA-A∗02:01 was found to be significantly associated with a lower risk of AED-induced SJS (OR = 0.36; 95 % CI: 0.13–0.97), while HLA-A∗24:02 and HLA-B∗15:02 were associated with an increased risk of AED-induced SJS (OR = 3.60; 95 % CI: 1.21–10.72 and OR = 4.41; 95 % CI: 1.18–16.47, respectively). For AED-induced TEN, HLA-A∗01:02 , HLA-B∗15:02, and HLA-B∗52:01 showed significant associations (OR = 6.92; 95 % CI: 1.39–34.37 and OR = 6.55; 95 % CI: 1.62–26.52, respectively), with HLA-DRB1∗03:01 being highly significant (OR = 5.09; 95 % CI: 1.72–15.00). Additionally, HLA-B∗40:02 was strongly associated with AED-induced DRESS (OR = 29.33; 95 % CI: 3.50–245.32). Conclusion This study identifies key HLA alleles associated with AED-induced SCARs in the Iraqi population. These findings could facilitate personalized medicine approaches, aiding in better prediction and prevention of SCARs in AED therapy.

Source: Heliyon

DOI: 10.1016/j.heliyon.2024.e41108

Authors: Ali Fadhel Ahmed, Dzul Azri Mohamed Noor, Majeed Arsheed Sabbah, Nur Fadhlina Musa, Nur Aizati Athirah Daud

Institutions: Universiti Sains Malaysia, Nahrain University

Language: English

Topic: Drug-Induced Adverse Reactions

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,100