The Phe-124-Cys and A-161T Variants of the Human 5-HT1BReceptor Gene Are Not Major Determinants of the Clinical Response to Sumatriptan
| Autor: | Antoinette MaassenVanDenBrink, Kaate R J Vanmolkot, Rune R. Frants, Michel D. Ferrari, Suneet Mehrotra, Arn M. J. M. van den Maagdenberg |
|---|---|
| Přispěvatelé: | Internal Medicine |
| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Agonist medicine.medical_specialty medicine.drug_class Migraine Disorders Phenylalanine Receptor expression DNA Mutational Analysis Gene Frequency Polymorphism (computer science) Internal medicine Humans Medicine Cysteine Receptor 5-HT receptor Aged Sumatriptan business.industry Genetic Variation Middle Aged musculoskeletal system medicine.disease Serotonin Receptor Agonists Treatment Outcome Endocrinology Neurology Migraine Pharmacogenetics Receptor Serotonin 5-HT1B cardiovascular system Female Neurology (clinical) business medicine.drug |
| Zdroj: | Headache, 47(5), 711-716. Wiley-Blackwell Publishing Ltd |
| ISSN: | 1526-4610 0017-8748 |
| DOI: | 10.1111/j.1526-4610.2007.00792.x |
| Popis: | Background.—The 5-HT1B/1D receptor 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-HT1B receptor play a major role in the therapeutic response to sumatriptan. The 5-HT1B receptor 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-HT1B receptor 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-HT1B receptor 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-HT1B receptor are major determinants in the clinical response to sumatriptan. |
| Databáze: | OpenAIRE |
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