TY - JOUR

T1 - Cluster headache polygenetic risk and known functional variants of CYP3A4 are not associated with treatment response

AU - Petersen, Anja Sofie

AU - Barloese, Mads

AU - Lund, Nunu

AU - Pedersen, Adam Friis

AU - Søborg, Marie Louise Kulas

AU - Chalmer, Mona Ameri

AU - Callesen, Ida

AU - Winsvold, Bendik Slagsvold

AU - Zwart, John Anker

AU - Ostrowski, Sisse Rye

AU - Pedersen, Ole Birger

AU - Sellebjerg, Finn

AU - Søndergaard, Helle Bach

AU - Hansen, Malene Bredahl

AU - Jensen, Rigmor Højland

AU - Hansen, Thomas Folkmann

AU - DBDS Genomic Consortium

N1 - Publisher Copyright: © 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

PY - 2023

Y1 - 2023

N2 - Background and purpose: The response to cluster headache treatments has a high interindividual variation. To date, treatment response has only been assessed by a candidate gene approach and no investigations into metabolic pathways have been performed. Our aim was to investigate the association between the 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, it was aimed to replicate previous single nucleotide polymorphisms found to be associated with treatment response in cluster headache and/or migraine. Methods: In, 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. Results: Inferior treatment response to oxygen, triptans and verapamil is associated with chronicity of cluster headache were confirmed but no evidence was found that a response could be predicted by a high genetic risk of cluster headache. Likewise, verapamil response was not associated with functional variants of CYP3A4. No support of the genetic variants previously reported to be associated with treatment response to triptans or verapamil was found. Conclusion: The clinically relevant variation in treatment response for cluster headache was not influenced by genetic factors in the present study.

AB - Background and purpose: The response to cluster headache treatments has a high interindividual variation. To date, treatment response has only been assessed by a candidate gene approach and no investigations into metabolic pathways have been performed. Our aim was to investigate the association between the 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, it was aimed to replicate previous single nucleotide polymorphisms found to be associated with treatment response in cluster headache and/or migraine. Methods: In, 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. Results: Inferior treatment response to oxygen, triptans and verapamil is associated with chronicity of cluster headache were confirmed but no evidence was found that a response could be predicted by a high genetic risk of cluster headache. Likewise, verapamil response was not associated with functional variants of CYP3A4. No support of the genetic variants previously reported to be associated with treatment response to triptans or verapamil was found. Conclusion: The clinically relevant variation in treatment response for cluster headache was not influenced by genetic factors in the present study.

KW - cluster headache

KW - cytochrome P450 3A

KW - oxygen

KW - polygenetic risk score

KW - sumatriptan

KW - verapamil

U2 - 10.1111/ene.15736

DO - 10.1111/ene.15736

M3 - Journal article

C2 - 36773010

AN - SCOPUS:85150291589

VL - 30

SP - 1425

EP - 1434

JO - European Journal of Neurology

JF - European Journal of Neurology

SN - 1351-5101

IS - 5

ER -