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Using a Genetic Risk Score Approach to Predict Headache Response to Triptans in Migraine Without Aura
Author(s) -
Cargnin Sarah,
Viana Michele,
Sances Grazia,
Cantello Roberto,
Tassorelli Cristina,
Terrazzino Salvatore
Publication year - 2019
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.1320
Subject(s) - triptans , aura , migraine with aura , medicine , logistic regression , rizatriptan , single nucleotide polymorphism , migraine , genome wide association study , genotype , genetics , biology , sumatriptan , agonist , gene , receptor
A large meta‐analysis of genome‐wide association studies has recently identified a number of risk loci for migraine without aura (MwoA). In this study, we tested the hypothesis that a genetic risk score based on single‐nucleotide polymorphisms (SNPs), previously reported to be associated with MwoA at genome‐wide significance, may influence headache response to triptans in patients with migraine without aura. Genotyping of rs9349379, rs2078371, rs6478241, rs11172113, rs1024905, and rs6724624 was conducted with a real‐time PCR allelic discrimination assay in 172 MwoA patients, of whom 36.6% were inconsistent responders to triptans. Each genetic risk score model was constructed as an unweighted score, calculated by adding the number of risk alleles for MwoA across each SNP at selected loci. The association with headache response to triptans was evaluated by logistic regression analysis adjusted for triptan, and the P values were corrected for the false discovery rate. The genetic risk score including susceptibility risk alleles at TRPM8 rs6724624 and FGF6 rs1024905 was found to be inversely associated with risk of inconsistent response to triptans (OR, 0.62; 95%CI, 0.43‐0.89; false discovery rate q value, 0.045). In addition, adding this genetic risk score to the triptan‐adjusted logistic regression model significantly improved ( P = .037) the discrimination accuracy, from 0.57 (95%CI, 0.50‐0.65) to 0.64 (95%CI, 0.57‐0.72). A modest but significant effect on risk of inconsistent response to triptans was identified for a genetic risk score model composed of 2 known risk alleles for MwoA, suggesting its potential utility in predicting headache response to triptan therapy.