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 - This article is protected by copyright. All rights reserved.
PY - 2023/5
Y1 - 2023/5
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/drug therapy
KW - Cytochrome P-450 CYP3A/genetics
KW - Genome-Wide Association Study
KW - Humans
KW - Tryptamines
KW - Verapamil/therapeutic use
KW - polygenetic risk score
KW - cytochrome P450 3A
KW - cluster headache
KW - verapamil
KW - oxygen
KW - sumatriptan
UR - http://www.scopus.com/inward/record.url?scp=85150291589&partnerID=8YFLogxK
U2 - 10.1111/ene.15736
DO - 10.1111/ene.15736
M3 - Journal article
C2 - 36773010
SN - 1351-5101
VL - 30
SP - 1425
EP - 1434
JO - European Journal of Neurology
JF - European Journal of Neurology
IS - 5
ER -