Do gene polymorphism in IL-1β, TNF-α and IL-6 influence therapeutic response in patients with drug refractory epilepsy?

Epilepsy Res. 2012 Sep;101(3):261-7. doi: 10.1016/j.eplepsyres.2012.04.013. Epub 2012 May 11.

Abstract

Purpose: Pro-inflammatory cytokines may play an important pathophysiological role in patients with epilepsy. To understand the role of genes encoding pro-inflammatory cytokines in epilepsy, this study aimed to evaluate the polymorphisms of the promoter regions of IL-1β-511C>T (rs16944), TNF-α-308G>A (rs1800629) and IL-6-174G>C (rs1800795) genes and to look into the interaction between these genes in influencing seizure susceptibility, seizure frequency and response to therapy.

Methods: The comparative frequency of polymorphism was determined in rs16944, rs1800629 and rs1800795 using PCR-RFLP in a group of 120 persons with epilepsy (PWE) and 110 ethnically matched healthy subjects of comparable age and sex in the North Indian population.

Results: Alleles and genotypes of rs16944, rs1800629 and rs1800795 were not found to influence the odds ratio of having susceptibility to epilepsy. Also gene-gene interaction of possible nine combinations of these genes did not show any positive association with epilepsy. The genotype and allelic frequency of rs1800795 showed a significant association (p<0.05) in seizure frequency (number of seizures/6-months) and drug refractory epilepsy. However, the genotype and allelic frequency of rs16944 and rs1800629 were not found to have such effect.

Conclusion: This study demonstrates that the rs16944, rs1800629 and rs1800795 polymorphism does not act as a strong susceptibility factor for epilepsy in North Indian population. The genotypic association of rs1800795 with seizure frequency and drug-refractory epilepsy raises the issue that a specific set of polymorphic genes can influence seizures and therapeutic response in epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Child
  • Epilepsy / drug therapy*
  • Epilepsy / genetics*
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • India
  • Interleukin-1beta / genetics*
  • Interleukin-6 / genetics*
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Polymorphism, Genetic*
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / genetics*
  • White People / genetics

Substances

  • Interleukin-1beta
  • Interleukin-6
  • Tumor Necrosis Factor-alpha