High-resolution HLA genotyping and severe cutaneous adverse reactions in lamotrigine-treated patients

Abstract

No single major HLA-related genetic risk factor was identified for lamotrigine-induced SCARs in patients of European origin. Only suggestive evidence was obtained for B*5801, A*6801, Cw*0718, DQB1*0609, and DRB1*1301. Confirmation of these results in a larger, independent sample is needed to determine whether any of the HLA alleles identified are truly associated with the development of lamotrigine-induced SCARs.

Genetic and immune predictors for hypersensitivity syndrome to antiepileptic drugs

“…49,50,82 No association was found between LTG-SJS/TEN and HLA-B*1502 in Chinese, 68 or European patients. 58 In our study, we observed that negative HLA-B*1502 does not predict negative LTG-HSR. We conclude that HLA-B*1502-negative status is not protective against LTG-HSR.…”

“…53 The parental drug was added at its therapeutic concentration. 53 The HLA polymorphism was determined using the method described by Kazeem et al 58 Enzyme-linked immunosorbent assay (ELISA) immunoassay kits for human IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, MCP1, regulated upon activation normal T-cell expressed and secreted (RANTES) and TNF-α (e-Bioscience, San Diego, CA, USA), as well as Fas, cleaved caspase 8, M30-Apoptosense ELISA (Bender MedSystems, Vienna, Austria) were used for quantitative determination. We used standards and reference reagents available from Bender MedSystems (Vienna, Austria).…”

Genome-wide association study of serious blistering skin rash caused by drugs

“…25 Associations were tested using two tails permuted (100 000 times) Fisher's exact analysis using PLINK software, by considering duplications and deletions separately. 16 We also investigated singleton CNVs 4100 kb 26 to find evidence for individual predisposition to SJS/TEN. For this analysis, we adopted a coverage cutoff excluding all CNVs that had coverage 420 genetic markers/CNVs.…”

“…Cases were defined by Kazeem et al 16 All cases and controls were epilepsy patients treated with lamotrigine and recruited retrospectively. Cases were patients who developed SJS/TEN or hypersensitivity reactions (although only SJS/TEN cases are included in this study), whereas controls were patients exposed to lamotrigine without developing SJS/TEN.…”

“…This study was based on three SJS/TEN collections: PGX40001, 15 LAM30004 16 and an Italian collection (Materials and methods). Both PGX40001 and Italian cases were induced by multiple drugs (Tables 1a and b), whereas all LAM30004 case were because of lamotrigine.…”