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The use of lamotrigine ( LTG) can be limited by the occurrence of cutaneous adverse drug reactions (c ADRs) that range from maculopapular eruption ( MPE) to the more severe Stevens-Johnson syndrome and toxic epidermal necrolysis. A few human leukocyte antigen ( HLA)-related genetic risk factors for carbamazepine-induced cADR have been identified. However, the HLA-related genetic risk factors associated with LTG-induced cADR are not yet well known. We performed HLA genotyping in 50 Korean patients with epilepsy, including 21 patients presenting LTG-induced MPE and 29 LTG-tolerant patients. A significant association between the HLA-A*2402 allele and LTG-induced MPE was identified, in comparison with the LTG-tolerant group (odds ratio [ OR] 4.09, p = 0.025) and the general Korean population ( OR 3.949, p = 0.005). The frequencies of the Cw*0102 or Cw*0702 alleles were significantly higher in the LTG- MPE group than in the Korean population, whereas the frequency of the A*3303 allele was lower. The coexistence of the A*2402 and Cw*0102 alleles was significantly associated with the LTG- MPE group when compared to the LTG-tolerant group ( OR 7.88, p = 0.007). In addition, the Cw*0701 allele was more frequent in the LTG-tolerant group than in the Korean population. These findings suggest the presence of HLA-related genetic risk factors for LTG-induced MPE in the Korean population. [ABSTRACT FROM AUTHOR]

Summary: Background: Although the US FDA recommends screening for HLA-B*1502 allele in most of Asian ancestry before initiating carbamazepine therapy, the HLA associations with carbamazepine hypersensitivity in non-Chinese Asian populations remain unclear. This study investigated the association between the HLA class I genotype and carbamazepine-induced severe cutaneous adverse reaction (SCAR) in Koreans. Methods: Twenty-four patients who had developed carbamazepine-induced SCAR (7 Stevens–Johnson syndrome (SJS), 17 drug hypersensitivity syndrome (HSS)), 50 carbamazepine-tolerant controls from the Korean Pharmacogenetic Adverse Drug Reaction Research Network and data of 485 Korean general population from a previously published study were recruited. HLA-A, -B, and -C genotyping was performed by direct DNA sequence analysis. Results: Only one of the seven SJS patients was positive for the B*1502 allele, but the frequency of B*1511 was much higher in the patients with CBZ-SJS than in the CBZ-tolerant control patients (P =0.011, P c =not significant; OR=18.0(2.3–141.2)). The frequencies of A*3101 in carbamazepine-induced HSS and SCAR were significantly higher than those in carbamazepine-tolerant controls (P c =0.011, OR=8.8(2.5–30.7) and P c =0.013, OR=7.3(2.3–22.5), respectively). The frequencies of B*1511 in carbamazepine-SJS and A*3101 in carbamazepine-HSS/SCAR were significantly higher than those in the general population. Conclusions: HLA-B*1502 does not seem to be an effective predictive marker for carbamazepine-induced SCAR, while HLA-B*1511 and A*3101 was associated with carbamazepine-induced SJS and HSS/SCAR respectively in the Korean population. [ABSTRACT FROM AUTHOR]