title: Frequencies of UGT1A4*2 (P24T) and *3 (L48V) and their effects on serum concentrations of lamotrigine.
abstract: The gene encoding uridine diphosphate glucuronosyltransferase (UGT) 1A4 shows considerable polymorphism. Several common drugs are metabolised by UGT1A4, among them lamotrigine (LTG). Experimental and clinical studies suggest that certain variants of UGT1A4 are associated with altered enzyme activity. However, results are conflicting. This clinical study aimed to investigate the frequencies of two common UGT1A4 variants, *2 (P24T) and *3 (L48V), and their potential effects on serum concentrations of LTG. The *2 variant was associated with a trend towards higher serum concentrations, while the *3 variant was associated with significantly lower serum concentrations of LTG. The calculated allele frequencies were in the same range as in earlier studies on Caucasian populations. To our knowledge, this is the first study suggesting a clinical effect of UGT1A4*2. Further study is needed to confirm this finding.
authors.affiliation: Department of Clinical Pharmacology, St. Olavs University Hospital, Trondheim, Norway. arne.reimers@legemidler.no.|Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. arne.reimers@legemidler.no.
authors.forename: Arne
authors.initials: A
authors.lastname: Reimers
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.|Department of Pathology and Medical Genetics, St. Olavs University Hospital, Trondheim, Norway.
authors.forename: Wenche
authors.initials: W
authors.lastname: Sjursen
authors.affiliation: Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Grethe
authors.initials: G
authors.lastname: Helde
authors.affiliation: Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.|Department of Neurology and Clinical Neurophysiology, St. Olavs University Hospital, Trondheim, Norway.
authors.forename: Eylert
authors.initials: E
authors.lastname: Brodtkorb
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014227:Triazines / Q000097:blood* / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D014227:Triazines; C019787:bilirubin glucuronoside glucuronosyltransferase; D014453:Glucuronosyltransferase; D000077213:Lamotrigine
keywords: Glucuronidation; Lamotrigine; Polymorphisms; Serum concentration; UGT1A4