G protein beta3 polymorphism and triptan response in cluster headache

Clin Pharmacol Ther. 2007 Oct;82(4):396-401. doi: 10.1038/sj.clpt.6100159. Epub 2007 Mar 14.


Only about 70% of migraine and cluster headache (CH) patients report significant treatment responses to triptans, which are agonists at 5-HT(1B/D) receptors belonging to the family of G protein-coupled receptors. We analyzed whether a common polymorphism in the gene for the G protein beta3 subunit (GNB3 C825T) modulates responder rates to triptans among a cohort of 231 unrelated Caucasian CH patients. A total of 180 CH patients used triptans, of whom 71.1% reported treatment success. The adjusted odds ratio for treatment response to triptans for heterozygous carriers of the GNB3 825T allele was 2.96 (95% confidence interval 1.34-6.56; P=0.0074) vs carriers of the 825CC genotype. The GNB3 genotype status did not affect responses to other acute and preventive therapeutic regimes including oxygen, verapamil, and corticosteroids, i.e., drugs not directly affecting G proteins. We conclude that pain relief by triptans is significantly modulated by a common genetic GNB3 variant.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cluster Headache / drug therapy*
  • Cluster Headache / genetics
  • Cluster Headache / metabolism
  • Dopamine Agonists / pharmacology
  • Dopamine Agonists / therapeutic use*
  • Female
  • Gene Frequency
  • Genotype
  • Germany
  • Heterotrimeric GTP-Binding Proteins / genetics*
  • Heterotrimeric GTP-Binding Proteins / metabolism
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Patient Selection
  • Polymorphism, Genetic*
  • Prospective Studies
  • Receptor, Serotonin, 5-HT1B / metabolism
  • Receptor, Serotonin, 5-HT1D / metabolism
  • Serotonin 5-HT1 Receptor Agonists*
  • Surveys and Questionnaires
  • Treatment Outcome
  • Tryptamines / pharmacology
  • Tryptamines / therapeutic use*
  • White People / genetics


  • Dopamine Agonists
  • G-protein beta3 subunit
  • Receptor, Serotonin, 5-HT1B
  • Receptor, Serotonin, 5-HT1D
  • Serotonin 5-HT1 Receptor Agonists
  • Tryptamines
  • Heterotrimeric GTP-Binding Proteins