ArticleMolecular genetics & genomic medicine2021
Genetic variants related to successful migraine prophylaxis with verapamil.
Article in Molecular genetics & genomic medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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Who cites it
5 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- Calcium Ions in the Physiology and Pathology of the Central Nervous System.International journal of molecular sciences · 2024Review
- Serum microRNA qPCR profiling and validation indicate upregulation of circulating miR-145-5p and miR-26a-5p in migraineurs.The journal of headache and pain · 2024Article
- Genetics of migraine: where are we now?The journal of headache and pain · 2023Review
- Pharmacogenetics in Primary Headache Disorders.Frontiers in pharmacology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCurrently, there is no biologically based rationale for drug selection in migraine prophylactic treatment.
methodsTo investigate the genetic variation underlying treatment response to verapamil prophylaxis, we selected 225 patients from a longitudinally established, deeply phenotyped migraine database (N = 5983), and collected uninterrupted quantitated verapamil treatment response data and DNA for these 225 cases. We recorded the number of headache days in the four weeks preceding treatment with verapamil and for four weeks, following completion of a treatment period with verapamil lasting at least five weeks. Whole-exome sequencing (WES) was applied to a discovery cohort consisting of 21 definitive responders and 14 definitive non-responders, and the identified single nucleotide polymorphisms (SNPs) showing significant association were genotyped in a separate confirmation cohort (185 verapamil treated patients). Statistical analysis of the WES data from the discovery cohort identified 524 SNPs associated with verapamil responsiveness (p < 0.01); among them, 39 SNPs were validated in the confirmatory cohort (n = 185) which included the full range of response to verapamil from highly responsive to not responsive.
resultsFourteen SNPs were confirmed by both percentage and arithmetic statistical approaches. Pathway and protein network analysis implicated myo-inositol biosynthetic and phospholipase-C second messenger pathways in verapamil responsiveness, emphasizing the earlier pathogenic understanding of migraine. No association was found between genetic variation in verapamil metabolic enzymes and treatment response.
conclusionOur findings demonstrate that genetic analysis in well-characterized subpopulations can yield important pharmacogenetic information pertaining to the mechanism of anti-migraine prophylactic medications.
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