The response to cluster headache treatments has a high interindividual variation. To date, treatment response has only been assessed by candidate gene approach and no investigations into metabolic pathways have been performed. To investigate the association between polygenetic risk of cluster headache and treatment response to first line cluster headache treatments as well as known functional variants of CYP3A4 and the response to verapamil. Further, to replicate previous single nucleotide polymorphisms found to be associated with treatment response in cluster headache and/or migraine.
508 cluster headache patients diagnosed according to the International Classification of Headache Disorders were genotyped and participated in a semi-structured interview to evaluate treatment response. Polygenetic risk scores were calculated by the effect retrieved from a meta-analysis of the latest two genome-wide association studies on cluster headache.
We confirmed previous findings, that inferior treatment response to oxygen, triptans and verapamil is associated with chronicity of cluster headache but found no evidence that a response could be predicted by a high genetic risk of cluster headache. Likewise, verapamil response did not associate with functional variants of CYP3A4. We found no support of the genetic variants previously reported to be associated with treatment response to triptans or verapamil.
The clinically relevant variation in treatment response for cluster headache was not influenced by genetic factors in the present study.

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