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No association between non-bullous skin reactions from lamotrigine and heterozygosity of UGT1A4 genetic variants *2(P24T) or *3(L48V) in Norwegian patients

Shirzadi, Maryam ; Reimers, Arne LU ; Helde, Grethe ; Sjursen, Wenche and Brodtkorb, Eylert (2017) In Seizure 45. p.169-171
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... (More)

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.

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author
; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Cutaneous adverse reaction, Lamotrigine, Polymorphisms, Serum concentration, UGT1A4
in
Seizure
volume
45
pages
3 pages
publisher
Elsevier
external identifiers
  • pmid:28068583
  • scopus:85008440361
ISSN
1059-1311
DOI
10.1016/j.seizure.2016.12.015
language
English
LU publication?
no
additional info
Publisher Copyright: © 2017 British Epilepsy Association
id
0140df44-b0c7-4a01-9e11-34f3eef0f670
date added to LUP
2024-08-31 14:43:21
date last changed
2024-09-02 08:24:12
@article{0140df44-b0c7-4a01-9e11-34f3eef0f670,
  abstract     = {{<p>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.</p>}},
  author       = {{Shirzadi, Maryam and Reimers, Arne and Helde, Grethe and Sjursen, Wenche and Brodtkorb, Eylert}},
  issn         = {{1059-1311}},
  keywords     = {{Cutaneous adverse reaction; Lamotrigine; Polymorphisms; Serum concentration; UGT1A4}},
  language     = {{eng}},
  month        = {{02}},
  pages        = {{169--171}},
  publisher    = {{Elsevier}},
  series       = {{Seizure}},
  title        = {{No association between non-bullous skin reactions from lamotrigine and heterozygosity of UGT1A4 genetic variants *2(P24T) or *3(L48V) in Norwegian patients}},
  url          = {{http://dx.doi.org/10.1016/j.seizure.2016.12.015}},
  doi          = {{10.1016/j.seizure.2016.12.015}},
  volume       = {{45}},
  year         = {{2017}},
}