Abstract
BackgroundTriptans are only effective in terminating cluster headache (CH) attacks in 70-80% of patients. Pharmacogenetic aspects of the serotonin metabolism, specifically variation in the 5-HTTLPR may be involved.MethodsGenetic association study in a well-defined cohort of 148 CH patients with information on drug response to triptans. CH was diagnosed according to the criteria of the International Headache Society. Genotypes of the 43-bp insdel (rs4795541) and A > G (rs25531) polymorphisms in the 5-HTTLPR promoter region were detected by restriction fragment length polymorphism analysis. We used logistic regression analysis to investigate the association between bi-allelic and tri-allelic genotypes and triptan non-response with genotype models.ResultsMean age at study entry among patients was 44.6 ± 10.5 years, 77.7% were men. The genotype distribution both for the bi-allelic and the tri-allelic polymorphism was in Hardy-Weinberg equilibrium. We did not find an association of the bi-allelic polymorphism with triptan non-response. While the effect estimates for the S variant of the tri-allelic polymorphisms suggested increased odds of triptan non-response in CH patients (multivariable-adjusted odds ratio [95% confidence interval]: L*L* genotype—reference; L*S* genotype—1.33 [0.53-3.32]; S*S* genotype—1.46 [0.54-3.98]), the results were not statistically significant.ConclusionsData from our study do not indicate a role of bi-allelic and tri-allelic genotypes of the 5-HTTLPR polymorphism in triptan non-response in CH.
Highlights
Triptans are only effective in terminating cluster headache (CH) attacks in 70-80% of patients
The mode of action may suggest that a lack of serotonin in the synaptic cleft or an insufficient stimulation of serotonin receptors plays an important role during CH attacks
Based on pathophysiological considerations and mode of action of triptans we investigated the association of the bi-allelic and tri-allelic 5-HTTLPR polymorphisms and triptan non-response in a cohort of well characterized CH patients
Summary
Triptans are only effective in terminating cluster headache (CH) attacks in 70-80% of patients. Triptans are 5-hydroxytriptamine (HT, serotonin) receptor agonists targeting the 5-HT1B/1D receptor subtypes with proven effectiveness in terminating acute CH attacks [3,4]. In humans the 5-HTT is encoded by the gene SLC6A4, which carries several polymorphisms in its promoter region (5-HTTLPR, 5-HTT linked polymorphic region) affecting transcription of the gene. Among those are a 43-bp insertion/deletion (insdel) polymorphism (rs4795541) [8] and a single nucleotide polymorphismus (SNP; rs25531) [9], which are located in close proximity to each other. The SNP rs25531 leads to an A → G exchange, which further modulates transcriptional activity
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