The Phe-124-Cys and A-161T variants of the human 5-HT1B receptor gene are not major determinants of the clinical response to sumatriptan
Background. - The 5-HT1B/1Dreceptor agonist sumatriptan is highly effective in the treatment of migraine. However, some patients do not respond to sumatriptan or experience recurrence of the headache after initial relief. In addition, some patients report chest symptoms after the use of sumatriptan. Objective. - To assess whether 2 genetic variants (F124C changing a phenylalanine for a cysteine and polymorphism A/T at nucleotide position -161 in the 5′ regulatory region) of the 5-HT1Breceptor play a major role in the therapeutic response to sumatriptan. The 5-HT1Breceptor most likely mediates the therapeutic action and coronary side effects of sumatriptan, and both F124C and A-161T have relevant functional consequences on either the affinity of sumatriptan to bind to the 5-HT1Breceptor or on receptor expression level itself, respectively. Method. - Genomic DNA of a relatively small but very well-characterized set of migraine patients with consistently good response to sumatriptan (n = 14), with no response (n = 12), with recurrence of the headache (n = 12), with chest symptoms (n = 13), and patients without chest symptoms (n = 27) was available for the genetic analyses and screened for the F124C variant and the A-161T polymorphism in the human 5-HT1Breceptor gene. Results. - F124C was not detected in any of the patients studied. In addition, we did not observe drastic changes in allele frequencies of the A-161T polymorphism that might hint to a causal relation with the therapeutic effect of sumatriptan. Conclusion. - We have not obtained any evidence that variants F124C and A-161T of the 5-HT1Breceptor are major determinants in the clinical response to sumatriptan.
|Keywords||1B, 5-HT, Migraine, Polymorphism, Sumatriptan, receptor|
|Persistent URL||dx.doi.org/10.1111/j.1526-4610.2007.00792.x, hdl.handle.net/1765/35427|
Mehrotra, S., Vanmolkot, K.R.J., Frants, R.R., Dichgans, M., Ferrari, M.D., & MaassenVanDenBrink, A.. (2007). The Phe-124-Cys and A-161T variants of the human 5-HT1B receptor gene are not major determinants of the clinical response to sumatriptan. Headache: the journal of head and face pain, 47(5), 711–716. doi:10.1111/j.1526-4610.2007.00792.x