5-hydroxytryptamine1B receptor and triptan response in migraine, lack of association with common polymorphisms.
Triptans mediate vasoconstriction of meningeal vessels via stimulation of vascular 5-hydroxytryptamine (5-HT)(1B) receptors. These drugs are recommended for acute treatment in patients with moderate-to-severe migraine attacks and in those patients with mild-to-moderate headache that are not controlled adequately by other agents. Yet, approximately 25% of all migraine users and 40% of all attacks do not respond to triptan treatment. Among the hypothesis to explain this is the possibility that genetic single nucleotide polymorphisms that alter the receptor, for example changing the transcriptional rate and therefore the amount of target protein might change the clinical response to these drugs. In the present contribution, we therefore decided to evaluate whether single nucleotide polymorphisms on the 5-HT(1B) gene might contribute to inter-individual variability in clinical responses to triptans. Two polymorphisms in the promoter region of the 5-HT(1B) receptor (T-261G and A-161T) and the synonymous variation G861C in the coding region were genotyped by restriction fragment length polymorphism in 105 migraine patients. In our sample population, 71% of patients responded to triptans. Allelic and diplotype frequencies were not significantly different between responders and non-responders. On the other hand, extrapolation of in vitro data on promoter activity would suggest that patients with higher copy number of receptors respond slightly better. Our data therefore do not support the involvement of 5-HT(1B) single nucleotide polymorphisms in mediating the inter-individual variability to triptans.
Velati
Daniela
D
DiSCAFF and DFB Center, Via Bovio, 6, 28100 Novara, Italy.
Viana
Michele
M
Cresta
Stefania
S
Mantegazza
Paola
P
Testa
Lucia
L
Bettucci
Diego
D
Rinaldi
Maurizio
M
Sances
Grazia
G
Tassorelli
Cristina
C
Nappi
Giuseppe
G
Canonico
Pier Luigi
PL
Martignoni
Emilia
E
Genazzani
Armando A
AA
D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020325:Migraine with Aura / Q000188:drug therapy* / Q000235:genetics; D020326:Migraine without Aura / Q000188:drug therapy* / Q000235:genetics; D016366:Open Reading Frames; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014363:Tryptamines / Q000494:pharmacology*
D044302:Receptor, Serotonin, 5-HT1B; D017366:Serotonin Receptor Agonists; D014363:Tryptamines