Shirzadi Maryam, Reimers Arne, Helde Grethe, Sjursen Wenche, Brodtkorb Eylert
Department of Neurology and Clinical Neurophysiology, St Olav's Hospital, Trondheim, Norway; Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
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.
Seizure. 2017 Feb;45:169-171. doi: 10.1016/j.seizure.2016.12.015. Epub 2016 Dec 22.
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.
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.
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).
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.
较高的初始血清浓度会增加皮肤不良反应的风险。主要代谢同工酶尿苷二磷酸葡萄糖醛酸转移酶（UGT）1A4的基因变异会影响拉莫三嗪（LTG）的消除。我们的目的是研究两个研究最多的变异体2（P24T）和3（L48V）与LTG引起的非大疱性皮肤反应发生之间的潜在关联。
该研究纳入了29名有LTG引起的非大疱性皮肤反应病史的白种人患者。184名对LTG耐受至少三个月的受试者作为对照。通过对第1外显子第一部分进行测序，对所有患者和对照进行UGT1A4基因分型。由于罕见的基因变异，排除了6名对照。
29名出现LTG皮疹的受试者中有2名（7%）为UGT1A4 *2杂合子，而178名耐受对照中有23名（13%）（p=0.54）。29名出现LTG皮疹的受试者中有4名（14%）为UGT1A4 *3杂合子，而178名耐受对照中有25名（14%）（p=0.97）。
UGT1A4基因变异体2（P24T）或3（L48V）的杂合性不太可能影响接受LTG治疗的患者发生非大疱性皮肤反应的风险。
