Department of Psychiatry, Anam Hospital, Korea University of Medicine, Seoul, Korea.
Graduate School of Clinical Pharmacy, CHA University, Pocheon, Korea.
Basic Clin Pharmacol Toxicol. 2019 Feb;124(2):163-169. doi: 10.1111/bcpt.13120. Epub 2018 Oct 5.
Uridine 5'-diphospho-glucuronosyltransferases (UGTs) are involved in the metabolism of lamotrigine, but whether the UGT1A4 and UGT2B7 genetic polymorphisms affect lamotrigine concentration remains controversial. Thus, the objective of this meta-analysis was to analyse the influence of UGT1A4 and UGT2B7 genetic polymorphisms on lamotrigine concentration. Through searching, screening, selection, data extraction and quantitative analyses, the influence of UGT1A4 and UGT2B7 genetic polymorphisms on lamotrigine concentration-to-dose ratio (CDR) was assessed by meta-analysis of nine studies. Neither UGT1A4 70C>A nor 142T>G significantly affected lamotrigine CDR values (standardized difference in means [SDM] = 0.433, 95% confidence interval [CI] = -0.380-1.302; SDM = -0.458, 95% CI = -1.141-0.224, respectively). Only the UGT2B7 -161C>T homozygous variant had significantly higher CDR values than the wild-type (WT) and heterozygous variant (SDM = 0.634, 95% CI = 0.056-1.222). In conclusion, CDR of lamotrigine was significantly higher for the UGT2B7 -161C>T homozygous variant than for the WT and heterozygous variant. Thus, UGT2B7 -161C>T homozygous variant needs to receive reduced dose.
尿苷二磷酸葡萄糖醛酸基转移酶（UGTs）参与拉莫三嗪的代谢，但 UGT1A4 和 UGT2B7 基因多态性是否影响拉莫三嗪浓度仍存在争议。因此，本荟萃分析的目的是分析 UGT1A4 和 UGT2B7 基因多态性对拉莫三嗪浓度的影响。通过检索、筛选、选择、数据提取和定量分析，对 9 项研究进行荟萃分析，评估 UGT1A4 和 UGT2B7 基因多态性对拉莫三嗪浓度-剂量比（CDR）的影响。UGT1A4 70C>A 和 142T>G 均未显著影响拉莫三嗪 CDR 值（标准化均数差 [SMD] = 0.433，95%置信区间 [CI] = -0.380-1.302；SMD = -0.458，95%CI = -1.141-0.224）。只有 UGT2B7-161C>T 纯合变异体的 CDR 值明显高于野生型（WT）和杂合变异体（SMD = 0.634，95%CI = 0.056-1.222）。总之，与 WT 和杂合变异体相比，UGT2B7-161C>T 纯合变异体的拉莫三嗪 CDR 值明显更高。因此，UGT2B7-161C>T 纯合变异体需要减少剂量。
