Meta-analysis of the Influence of UGT Genetic Polymorphisms on Lamotrigine Concentration

Su Cheol Kim, Myeong Gyu Kim

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)163-169
Number of pages7
JournalBasic and Clinical Pharmacology and Toxicology
Volume124
Issue number2
DOIs
StatePublished - Feb 2019

Bibliographical note

Publisher Copyright:
© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society)

Keywords

  • drug metabolism
  • genetic polymorphism
  • lamotrigine
  • meta-analysis
  • uridine 5′-diphospho-glucuronosyltransferase

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