Using a Genetic Risk Score Approach to Predict Headache Response to Triptans in Migraine Without Aura

Cargnin, Sarah; Viana, Michele; Sances, Grazia; Cantello, Roberto; Tassorelli, Cristina; Terrazzino, Salvatore

doi:10.1002/jcph.1320

Cited by 15 publications

(10 citation statements)

References 41 publications

(89 reference statements)

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“…One particular use of GRS may be in understanding drug reactions and efficacy of therapies. Studies to predict response and efficacy of treatment with triptans in migraineurs have used this approach [250, 251]. While sensitivity and specificity are still relatively low, the diagnostic value of GRS will improve with the discovery of more SNPs.…”

Section: Main Textmentioning

confidence: 99%

Advances in genetics of migraine

2019

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BackgroundMigraine is a complex neurovascular disorder with a strong genetic component. There are rare monogenic forms of migraine, as well as more common polygenic forms; research into the genes involved in both types has provided insights into the many contributing genetic factors. This review summarises advances that have been made in the knowledge and understanding of the genes and genetic variations implicated in migraine etiology.FindingsMigraine is characterised into two main types, migraine without aura (MO) and migraine with aura (MA). Hemiplegic migraine is a rare monogenic MA subtype caused by mutations in three main genes - CACNA1A, ATP1A2 and SCN1A - which encode ion channel and transport proteins. Functional studies in cellular and animal models show that, in general, mutations result in impaired glutamatergic neurotransmission and cortical hyperexcitability, which make the brain more susceptible to cortical spreading depression, a phenomenon thought to coincide with aura symptoms. Variants in other genes encoding ion channels and solute carriers, or with roles in regulating neurotransmitters at neuronal synapses, or in vascular function, can also cause monogenic migraine, hemiplegic migraine and related disorders with overlapping symptoms. Next-generation sequencing will accelerate the finding of new potentially causal variants and genes, with high-throughput bioinformatics analysis methods and functional analysis pipelines important in prioritising, confirming and understanding the mechanisms of disease-causing variants.With respect to common migraine forms, large genome-wide association studies (GWAS) have greatly expanded our knowledge of the genes involved, emphasizing the role of both neuronal and vascular pathways. Dissecting the genetic architecture of migraine leads to greater understanding of what underpins relationships between subtypes and comorbid disorders, and may have utility in diagnosis or tailoring treatments. Further work is required to identify causal polymorphisms and the mechanism of their effect, and studies of gene expression and epigenetic factors will help bridge the genetics with migraine pathophysiology.ConclusionsThe complexity of migraine disorders is mirrored by their genetic complexity. A comprehensive knowledge of the genetic factors underpinning migraine will lead to improved understanding of molecular mechanisms and pathogenesis, to enable better diagnosis and treatments for migraine sufferers.

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Section: Main Textmentioning

confidence: 99%

Advances in genetics of migraine

2019

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“…Several previous studies have investigated the prediction of the outcome of migraine treatment. In patients with headache, genetic factors, migraine characteristics, and autonomic symptoms have been evaluated to predict treatment response to triptan and topiramate (26)(27)(28). In addition, white matter hyperintensity was found to predict migraine prognosis (29); however, the correlation and regression analysis between predictors and patient outcomes used in this previous study were insufficient.…”

Section: Discussionmentioning

confidence: 82%

Baseline Brain Gray Matter Volume as a Predictor of Acupuncture Outcome in Treating Migraine

Yang

Liu

et al. 2020

Front. Neurol.

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Background: The present study aimed to investigate the use of imaging biomarkers to predict the outcome of acupuncture in patients with migraine without aura (MwoA). Methods: Forty-one patients with MwoA received 4 weeks of acupuncture treatment and two brain imaging sessions at the Beijing Traditional Chinese Medicine Hospital affiliated with Capital Medical University. Patients kept a headache diary for 4 weeks before treatment and during acupuncture treatment. Responders were defined as those with at least a 50% reduction in the number of migraine days. The machine learning method was used to distinguish responders from non-responders based on pre-treatment brain gray matter (GM) volume. Longitudinal changes in GM predictive regions were also analyzed. Results: After 4 weeks of acupuncture, 19 patients were classified as responders. Based on 10-fold cross-validation for the selection of GM features, the linear support vector machine produced a classification model with 73% sensitivity, 85% specificity, and 83% accuracy. The area under the receiver operating characteristic curve was 0.7871. This classification model included 10 GM areas that were mainly distributed in the frontal, temporal, parietal, precuneus, and cuneus gyri. The reduction in the number of migraine days was correlated with baseline GM volume in the cuneus, parietal, and frontal gyri in all patients. Moreover, the left cuneus showed a longitudinal increase in GM volume in responders. Conclusion: The results suggest that pre-treatment brain structure could be a novel predictor of the outcome of acupuncture in the treatment of MwoA. Imaging features could be a useful tool for the prediction of acupuncture efficacy, which would enable the development of a personalized medicine strategy.

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“…Based on our lack of reproducibility and the inconclusive results from migraine, it is suggested that the rs2651899 is not a relevant predictor of triptan response. An Italian study [25] hypothesized that SNPs associated with migraine could influence triptan response and they found that rs6724624 and rs1024905 were inversely associated with inconsistent response to triptans. These findings were not replicated in our CH cohort, but the two SNPs have not been found to be associated with CH [12,13].…”

Section: Discussionmentioning

confidence: 99%

“…Previously, one SNP (rs5443) was associated with treatment response in CH [22] and four SNPs (rs6275, rs2651899, rs1024905 TA B L E 1 Background information on the study participants. and rs6724624) with triptan response in migraine [5,[23][24][25] (Table 4). Amongst the 395 CH patients who had tried triptans, 73.4% (n = 290) were classified as triptan responders.…”

Section: Replication Of Treatment Response With Previously Reported Snpsmentioning

confidence: 99%

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

Petersen

Barloese

Lund

et al. 2023

Euro J of Neurology

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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.

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Using a Genetic Risk Score Approach to Predict Headache Response to Triptans in Migraine Without Aura

Cited by 15 publications

References 41 publications

Advances in genetics of migraine

Advances in genetics of migraine

Baseline Brain Gray Matter Volume as a Predictor of Acupuncture Outcome in Treating Migraine

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

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