Pharmacogenomics predictors of aromatic antiepileptic drugs-induced SCARs in the Iraqi patients
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-medi...
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Elsevier
2025-01-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024171393 |
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| author | Ali Fadhel Ahmed Dzul Azri Mohamed Noor Majeed Arsheed Sabbah Nur Fadhlina Musa Nur Aizati Athirah Daud |
| author_facet | Ali Fadhel Ahmed Dzul Azri Mohamed Noor Majeed Arsheed Sabbah Nur Fadhlina Musa Nur Aizati Athirah Daud |
| author_sort | Ali Fadhel Ahmed |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c22fcbe9e98346388bef81ecd194f718 |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| spelling | doaj-art-c22fcbe9e98346388bef81ecd194f7182025-01-17T04:50:10ZengElsevierHeliyon2405-84402025-01-01111e41108Pharmacogenomics predictors of aromatic antiepileptic drugs-induced SCARs in the Iraqi patientsAli Fadhel Ahmed0Dzul Azri Mohamed Noor1Majeed Arsheed Sabbah2Nur Fadhlina Musa3Nur Aizati Athirah Daud4Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, USM Pulau Pinang, MalaysiaDiscipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, USM Pulau Pinang, MalaysiaForensic DNA for Research and Training Centre, Alnahrain University, Baghdad, 64074, IraqHuman Genome Centre, School of Medical Sciences, Universiti Sains Malaysia Health Campus, 16150, Kubang Kerian, Kelantan, MalaysiaDiscipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, USM Pulau Pinang, Malaysia; Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia; Corresponding author. Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, USM Pulau Pinang, Malaysia.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.http://www.sciencedirect.com/science/article/pii/S2405844024171393Severe cutaneous adverse reactionsSJSHLAPharmacogeneticsAED |
| spellingShingle | Ali Fadhel Ahmed Dzul Azri Mohamed Noor Majeed Arsheed Sabbah Nur Fadhlina Musa Nur Aizati Athirah Daud Pharmacogenomics predictors of aromatic antiepileptic drugs-induced SCARs in the Iraqi patients Heliyon Severe cutaneous adverse reactions SJS HLA Pharmacogenetics AED |
| title | Pharmacogenomics predictors of aromatic antiepileptic drugs-induced SCARs in the Iraqi patients |
| title_full | Pharmacogenomics predictors of aromatic antiepileptic drugs-induced SCARs in the Iraqi patients |
| title_fullStr | Pharmacogenomics predictors of aromatic antiepileptic drugs-induced SCARs in the Iraqi patients |
| title_full_unstemmed | Pharmacogenomics predictors of aromatic antiepileptic drugs-induced SCARs in the Iraqi patients |
| title_short | Pharmacogenomics predictors of aromatic antiepileptic drugs-induced SCARs in the Iraqi patients |
| title_sort | pharmacogenomics predictors of aromatic antiepileptic drugs induced scars in the iraqi patients |
| topic | Severe cutaneous adverse reactions SJS HLA Pharmacogenetics AED |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024171393 |
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