Chonlaphat SukasemSuthida SriritthaChonlawat ChaichanThapanat NakkrutPatompong SatapornpongKanoot JaruthamsophonThawinee JantararoungtongNapatrupron KoomdeeSadeep MedhasiSarawut Oo-PuthinanTicha RerkpattanapipatJettanong KlaewsongkramPawinee RerknimitrPapapit TuchindaLeena ChularojanamontriNapatra TovanabutraNaravut SuvannangThanyada RungrotmongkolSurasak SaokaewWichai AekplakornApichaya PuangpetchRamathibodi HospitalSiriraj HospitalFaculty of Tropical Medicine, Mahidol UniversityUniversity of PhayaoChulalongkorn UniversityFaculty of Medicine, Prince of Songkia UniversityRangsit UniversityNaresuan UniversityBumrungrad International HospitalFaculty of Medicine Ramathibodi Hospital, Mahidol UniversityMahidol UniversityFaculty of Medicine, Chulalongkorn UniversityChiang Mai UniversityTriamwitpattana schoolThe Thai Severe Cutaneous Adverse Drug Reaction (THAI-SCAR) Research GroupNeurological Institute of Thailand2022-08-042022-08-042021-12-01Pharmacogenomics Journal. Vol.21, No.6 (2021), 682-690147311501470269X2-s2.0-85108814525https://repository.li.mahidol.ac.th/handle/123456789/75931Aromatic antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs) add up to the limited use of the AEDs in the treatment and prevention of seizures. Human leukocyte antigen-B (HLA-B) alleles have been linked to AEDs-induced cADRs. We investigated the association between cADRs (including Stevens–Johnson syndrome; SJS/toxic epidermal necrolysis; TEN, drug reaction with eosinophilia and systemic symptoms; DRESS, and Maculopapular eruption; MPE) caused by AEDs (phenytoin, carbamazepine, lamotrigine, phenobarbital and oxcarbazepine) and HLA-B alleles in Thai population. Through the case-control study, 166 patients with AEDs-induced cADRs, 426 AEDs-tolerant patients (AEDs-tolerant controls), and 470 healthy subjects (Thai population) were collected. The HLA genotypes were detected using the polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. We also performed a meta-analysis with these data and other populations. The carrier rate of HLA-B*15:02 was significantly different between AEDs-induced cADRs group and AEDs-tolerant group (Odds ratio; OR 4.28, 95% Confidence interval; CI 2.64–6.95, p < 0.001), AEDs-induced cADRs group and Thai population (OR 2.15, 95%CI 1.41–3.29, p < 0.001). In meta-analysis showed the strong association HLA-B*15:02 with AEDs-induced cADRs (OR 4.77, 95%CI 1.79–12.73, p < 0.001). Furthermore, HLA-B*15:02 was associated with SJS/TEN induced by AEDs (OR 10.28, 95%CI 6.50–16.28, p < 0.001) Phenytoin (OR 4.12, 95%CI 1.77–9.59, p = 0.001) and carbamazepine (OR 137.69, 95%CI 50.97–371.98, p < 0.001). This study demonstrated that genetic association for AEDs-induced cADRs was phenotype-specific. A strong association between HLA-B*15:02 and AEDs-induced SJS/TEN was demonstrated with an OR of 10.79 (95%CI 5.50–21.16, p < 0.001) when compared with AEDs-tolerant group. On the other hand, the carrier rates of HLA-B*08:01, HLA-B*13:01, and HLA-B*56:02 were significantly higher in the DRESS group compared with the AEDs-tolerant group (p = 0.029, 0.007, and 0.017, respectively). The HLA-B*15:02 allele may represent a risk factor for AEDs-induced cADRs.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyPharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1038/s41397-021-00247-3