Department of Pharmacology, School of Medicine, University of Marmara, Istanbul, Turkey.
Epilepsy Res. 2011 Jun;95(1-2):1-8. doi: 10.1016/j.eplepsyres.2011.01.016. Epub 2011 May 20.
Lamotrigine (LTG) which has a widespread use in epilepsy treatment as an antiepileptic agent is metabolized by UDP-glucuronosyl transferase (UGT) enzymes. In this study, single nucleotide polymorphisms, P24T and L48V, of the UGT1A4 enzyme have been investigated in a Turkish population of patients with epilepsy (n=131) by comparing serum levels of LTG of wild type and polymorphic subjects. High performance liquid chromatography (HPLC) was used to measure serum concentrations of LTG. The P24T and L48V polymorphisms of the UGT1A4 enzyme were analyzed with a matrix assisted laser desorption-time of flight (MALDI-TOF) mass spectrometry method. The frequencies of the heterozygous alleles for L48V or P24T polymorphisms were 22.4% and 3.8%, respectively. L48V polymorphism was found to decrease the serum concentration of LTG in patients on monotherapy or polytherapy. The LTG levels of non smoking monotherapy patients were 52% lower for the L48V polymorphism than for wild type alleles. Also the LTG levels were significantly lower for non smoking or smoking polymorphic alleles than for normal. The high frequency of the L48V polymorphism detected in the Turkish population indicates that LTG dose adjustments in patients with the UGT1A4 L48V polymorphic enzyme should be taken into account.
左乙拉西坦（LTG）作为一种抗癫痫药物，广泛用于癫痫治疗，其代谢由 UDP-葡萄糖醛酸转移酶（UGT）酶完成。在这项研究中，通过比较野生型和多态性受试者的 LTG 血清水平，研究了土耳其癫痫患者（n=131）UGT1A4 酶的 P24T 和 L48V 单核苷酸多态性。采用高效液相色谱（HPLC）法测定 LTG 血清浓度。采用基质辅助激光解吸飞行时间（MALDI-TOF）质谱法分析 UGT1A4 酶的 P24T 和 L48V 多态性。L48V 或 P24T 多态性杂合等位基因的频率分别为 22.4%和 3.8%。L48V 多态性降低了单药或多药治疗患者的 LTG 血清浓度。与野生型等位基因相比，非吸烟单药治疗患者的 L48V 多态性 LTG 水平降低了 52%。此外，非吸烟或吸烟多态性等位基因的 LTG 水平明显低于正常水平。在土耳其人群中检测到 L48V 多态性的高频率表明，应考虑对 UGT1A4 L48V 多态性酶患者进行 LTG 剂量调整。
