Association of polymorphisms in NR1I2 and ABCB1 genes with epilepsy treatment responses

Pharmacogenomics. 2007 Sep;8(9):1151-8. doi: 10.2217/14622416.8.9.1151.

Abstract

Objectives: The aim of this study was to investigate whether the polymorphisms in the NR1I2 and ABCB1 genes were associated with epilepsy treatment responses.

Methods & results: NR1I2and ABCB1 polymorphisms were genotyped in 114 drug-resistant epileptic patients, 213 seizure-free patients and 287 normal controls. Highly specific real-time PCR was applied to detect the variants by using TaqMan allelic specific probe. For a single gene test, it was demonstrated that 3435C>T in the ABCB1 gene had a significant effect on epilepsy treatment responses, but polymorphisms in the NR1I2 gene did not. Further analysis using a logistic regression model revealed that only 2677G>T and 3435C>T in the ABCB1 gene and their interaction term were associated with drug-resistant epilepsy after adjustment for etiology and epilepsy classification. In the present study, the polymorphisms in the NR1I2 gene were not significantly associated with epilepsy treatment responses.

Conclusion: Our results indicated that 2677G>T and 3435C > T in the ABCB1 gene contributed to drug-resistant epilepsy. Although biologically plausible, the polymorphisms in NR1I2 investigated in the present study did not play a role in epilepsy treatment responses. Other unveiled genetic variants in the NR1I2 gene that may have the potential to affect ABCB1 gene expression are worth further investigation in future studies.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Adult
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / therapeutic use*
  • Epilepsy / classification
  • Epilepsy / drug therapy*
  • Genotype
  • Humans
  • Korea
  • Middle Aged
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide*
  • Pregnane X Receptor
  • Receptors, Steroid / genetics*
  • Reference Values
  • Treatment Outcome

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anticonvulsants
  • NR1I2 protein, human
  • Pregnane X Receptor
  • Receptors, Steroid