Association of cutaneous adverse drug reactions due to antiepileptic drugs with HLA alleles in a North Indian population

Purpose: Aromatic antiepileptic drugs (AEDs) are frequently implicated in cutaneous adverse drug reactions (cADRs), a few of which are associated with certain human leukocyte antigen (HLA) alleles in some populations. We aimed to find HLA-associations with AED-related cADRs among North Indians. Methods: North Indian subjects with cADR due to an AED, and those who were AED-tolerant were recruited as cases and controls, respectively. Genotyping for HLA-A, B and DRB1 were performed. Statistical analysis to compare carrier-rates and allele-frequencies between cases and controls (and healthy population, where necessary), was done for HLA-alleles occurring more than twice in either group. Results: 120 cases {11- Lamotrigine (LTG), 14-Valproic acid (VPA), 8-Levetiracetam (LEV), 35-Carbamazepine (CBZ) and 52- Phenytoin (PHT)}, and 250 controls were recruited. Presence of HLA-A(star)31:01 and HLA-B(star)51:01 were found to increase the risk of Maculopapular exanthema (MPE) due to CBZ and PHT (OR = 6.38; 95% CI: 1.46-27.75; OR = 4.60; 95% CI: 1.54-13.72, respectively). Among the severe cADRs, HLA-B(star)57:01(OR = 11.00 95% CI: 1.41-85.81) and HLA-DRB1(star)-07:01 (OR = 7.25; 95% CI: 1.09-48.18) were noted to be significantly associated with CBZ-induced Stevens Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN); HLA-B (star)51:01 was associated with drug reaction eosinophilia and systemic symptoms (DRESS) caused by PHT (OR = 6.90; 95% CI: 1.38-34.29). Conclusions: We found significant associations of some HLA alleles with specific cADRs to CBZ and PHT in North Indians, which may need to be tested before AED-initiation; only screening for HLA-B(star)15:02 may not help in this population.