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European Journal of Clinical Pharmacology

, Volume 70, Issue 8, pp 941–946 | Cite as

Correlation of the UGT1A4 gene polymorphism with serum concentration and therapeutic efficacy of lamotrigine in Han Chinese of Northern China

  • Ying Chang
  • Li-ya Yang
  • Meng-chao Zhang
  • Song-Yan LiuEmail author
Pharmacokinetics and Disposition

Abstract

Objective

The pharmacokinetics of lamotrigine (LTG) varies significantly among individuals and particularly among different ethnic groups. This is in part due to the presence of genetic polymorphisms affecting genes that metabolize LTG. UGT1A4 is a major metabolizing enzyme of LTG. The aim of this study was to investigate the effect of two UGT1A4 gene polymorphisms, UGT1A4 (70C > A) and UGT1A4 (142 T > G), on the levels and efficacy of LTG in Han Chinese patients with epilepsy.

Methods

The study cohort comprised 106 Han Chinese patients patients with epilepsy who were receiving LTG monotherapy. Blood samples were taken and LTG levels measured. The presence of UGT1A4 (70C > A) and UGT1A4 (142 T > G) was determined. The therapeutic efficacy of LTG at the 1-year time-point was assessed.

Results

All patients were homozygous for the CC genotype of UGT1A4 (70C > A), while the distribution of UGT1A4 (142 T > G) varied among patients. Two patients had a single nucleotide deletion at position 127 (UGT1A4 127delA). To evaluate the effect of the UGT1A4 (142 T > G) polymorphism on LTG pharmacokinetics, patients were divided into two groups. Group A included patients with the 142TG or 142GG polymorphism and Group B patients had the 142TT polymorphism. The normalized blood concentration and the efficacy of LTG were higher in Group B patients than in Group A patients (P < 0.05). The two patients with UGT1A4 127delA genotype had extremely high blood levels of LTG, and treatment was discontinued in one of these patients due to a severe LTG-associated rash.

Conclusion

Patients with the UGT1A4 142TT polymorphism had a higher blood LTG concentration and better therapeutic efficacy, suggesting that this polymorphism influences LTG activity. The UGT1A4 127delA polymorphism significantly affected LTG levels and increased one of our patient's susceptibility to LTG-related adverse events.

Keywords

Epilepsy Lamotrigine UGT1A4 Gene polymorphism Blood concentration 

Notes

Acknowledgments

This work is supported by grants from Jilin Province Science and Technology Program (3D511Z343430) and Basic Scientific Research Funds of Jilin University (450060491602).

Conflict of interest

None.

Supplementary material

228_2014_1690_MOESM1_ESM.docx (13 kb)
ESM 1 (DOCX 13 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Ying Chang
    • 1
  • Li-ya Yang
    • 1
  • Meng-chao Zhang
    • 1
  • Song-Yan Liu
    • 1
    Email author
  1. 1.China–Japan Union HospitalJilin UniversityChangchunChina

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