Maryam Shirzadi1, Arne Reimers2, Grethe Helde3, Wenche Sjursen4, Eylert Brodtkorb5. 1. Department of Neurology and Clinical Neurophysiology, St Olav's Hospital, Trondheim, Norway; Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway. Electronic address: maryam.shirzadi@gmail.com. 2. Department of Clinical Pharmacology, St Olav's Hospital, Trondheim, Norway; Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway. 3. Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway. 4. Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway; Department of Pathology and Medical Genetics, St Olav's Hospital, Trondheim, Norway. 5. Department of Neurology and Clinical Neurophysiology, St Olav's Hospital, Trondheim, Norway; Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
Abstract
PURPOSE: High initial serum concentrations increase the risk of cutaneous adverse reactions. Genetic variants of the main metabolizing isoenzyme, uridine diphosphate glucuronosyltransferase (UGT) 1A4 influence the elimination of lamotrigine (LTG). Our aim was to investigate the potential association between the two best studied variants, *2 (P24T) and *3 (L48V), and the occurrence non-bullous skin reactions from LTG. METHOD: The study included 29 patients of Caucasian ethnicity with a history of non-bullous skin reactions from LTG. 184 subjects tolerant to LTG for at least three months were used as controls. UGT1A4 genotyping was performed in all patients and controls by sequencing of the first part of exon 1. Six controls were excluded due to rare genetic variants. RESULTS: Two of 29 subjects (7%) with rash from LTG were heterozygous for UGT1A4 *2, compared to 23 of 178 (13%) tolerant controls (p=0.54). Four of 29 subjects (14%) with rash from LTG were heterozygous for UGT1A4 *3 compared to 25 of 178 (14%) tolerant controls (p=0.97). CONCLUSION: It is unlikely that heterozygosity of the UGT1A4 genetic variants *2(P24T) or *3(L48V) influences the risk of non-bullous skin reactions in patients treated with LTG.
PURPOSE: High initial serum concentrations increase the risk of cutaneous adverse reactions. Genetic variants of the main metabolizing isoenzyme, uridine diphosphate glucuronosyltransferase (UGT) 1A4 influence the elimination of lamotrigine (LTG). Our aim was to investigate the potential association between the two best studied variants, *2 (P24T) and *3 (L48V), and the occurrence non-bullous skin reactions from LTG. METHOD: The study included 29 patients of Caucasian ethnicity with a history of non-bullous skin reactions from LTG. 184 subjects tolerant to LTG for at least three months were used as controls. UGT1A4 genotyping was performed in all patients and controls by sequencing of the first part of exon 1. Six controls were excluded due to rare genetic variants. RESULTS: Two of 29 subjects (7%) with rash from LTG were heterozygous for UGT1A4 *2, compared to 23 of 178 (13%) tolerant controls (p=0.54). Four of 29 subjects (14%) with rash from LTG were heterozygous for UGT1A4 *3 compared to 25 of 178 (14%) tolerant controls (p=0.97). CONCLUSION: It is unlikely that heterozygosity of the UGT1A4 genetic variants *2(P24T) or *3(L48V) influences the risk of non-bullous skin reactions in patients treated with LTG.
Authors: Justine Badée; Stephen Fowler; Saskia N de Wildt; Abby C Collier; Stephan Schmidt; Neil Parrott Journal: Clin Pharmacokinet Date: 2019-02 Impact factor: 6.447