G protein beta3 polymorphism and triptan response in cluster headache.
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.
Schürks
M
M
Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Kurth
T
T
Stude
P
P
Rimmbach
C
C
de Jesus
J
J
Jonjic
M
M
Diener
H-C
HC
Rosskopf
D
D
D000328:Adult; D003027:Cluster Headache / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005858:Germany; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D018579:Patient Selection; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism; D044346:Receptor, Serotonin, 5-HT1D / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014363:Tryptamines / Q000494:pharmacology / Q000627:therapeutic use*; D044465:White People / Q000235:genetics
D018491:Dopamine Agonists; C454420:G-protein beta3 subunit; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D058825:Serotonin 5-HT1 Receptor Agonists; D014363:Tryptamines; D020962:Heterotrimeric GTP-Binding Proteins