title: No association between non-bullous skin reactions from lamotrigine and heterozygosity of UGT1A4 genetic variants *2(P24T) or *3(L48V) in Norwegian patients.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Maryam
authors.initials: M
authors.lastname: Shirzadi
authors.affiliation: 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.
authors.forename: Arne
authors.initials: A
authors.lastname: Reimers
authors.affiliation: Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Grethe
authors.initials: G
authors.lastname: Helde
authors.affiliation: 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.
authors.forename: Wenche
authors.initials: W
authors.lastname: Sjursen
authors.affiliation: Department of Neurology and Clinical Neurophysiology, St Olav's Hospital, Trondheim, Norway; Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Eylert
authors.initials: E
authors.lastname: Brodtkorb
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D007223:Infant; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D009664:Norway; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012871:Skin Diseases / Q000139:chemically induced*; D014227:Triazines / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014227:Triazines; C019787:bilirubin glucuronoside glucuronosyltransferase; D014453:Glucuronosyltransferase; D000077213:Lamotrigine
keywords: Cutaneous adverse reaction; Lamotrigine; Polymorphisms; Serum concentration; UGT1A4