TY - JOUR
T1 - The influence of genetic constitution on migraine drug responses
AU - Christensen, Anne Francke
AU - Esserlind, Ann-Louise
AU - Werge, Thomas
AU - Stefánsson, Hreinn
AU - Stefánsson, Kári
AU - Olesen, Jes
N1 - © International Headache Society 2015.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - Objective Specific acute treatments of migraine are 5HT1B/D receptor agonists; triptans and ergotamine, but only two-thirds of patients respond well without side effects. No migraine-prophylactic drugs are specific to migraine. Prophylactic drugs are selected by time-consuming âtrial and error.†Personalized treatment is therefore much needed. The objective of this study was to test the effect of 12 single nucleotide polymorphisms (SNPs) significantly associated with migraine on migraine drug responses. Methods Semi-structured migraine interviews including questions on drug responses, blood samples and genotyping were performed on 1806 unrelated migraine cases recruited from the Danish Headache Center. Association analyses were carried out using logistic regression, assuming an additive model for the genetic effect. The effect on drug responses was tested for a combined genetic score and for each of the 12 SNPs. Significant findings were subsequently tested in an independent replication sample of 392 unrelated Danish migraine cases. Results A single risk variant, rs2651899 in PRDM16, was significantly associated with efficacy of triptans with an odds ratio (OR) of treatment success of 1.3, and a higher combined genetic score was significantly associated with efficacy of triptans with an OR of success of up to 2.6. A number of SNPs showed nominal preferential association with the efficacy of triptans and others with prophylactic drugs. Analyses of triptans and ergotamine complemented each other and gave a stronger signal when analyzed together. The associations between response to triptans and genetic load and rs2651899 were partially confirmed in the independent sample. Conclusion We show for the first time an association between genetic constitution and migraine drug response. This is a first step toward future individualized medicine.
AB - Objective Specific acute treatments of migraine are 5HT1B/D receptor agonists; triptans and ergotamine, but only two-thirds of patients respond well without side effects. No migraine-prophylactic drugs are specific to migraine. Prophylactic drugs are selected by time-consuming âtrial and error.†Personalized treatment is therefore much needed. The objective of this study was to test the effect of 12 single nucleotide polymorphisms (SNPs) significantly associated with migraine on migraine drug responses. Methods Semi-structured migraine interviews including questions on drug responses, blood samples and genotyping were performed on 1806 unrelated migraine cases recruited from the Danish Headache Center. Association analyses were carried out using logistic regression, assuming an additive model for the genetic effect. The effect on drug responses was tested for a combined genetic score and for each of the 12 SNPs. Significant findings were subsequently tested in an independent replication sample of 392 unrelated Danish migraine cases. Results A single risk variant, rs2651899 in PRDM16, was significantly associated with efficacy of triptans with an odds ratio (OR) of treatment success of 1.3, and a higher combined genetic score was significantly associated with efficacy of triptans with an OR of success of up to 2.6. A number of SNPs showed nominal preferential association with the efficacy of triptans and others with prophylactic drugs. Analyses of triptans and ergotamine complemented each other and gave a stronger signal when analyzed together. The associations between response to triptans and genetic load and rs2651899 were partially confirmed in the independent sample. Conclusion We show for the first time an association between genetic constitution and migraine drug response. This is a first step toward future individualized medicine.
KW - Journal Article
U2 - 10.1177/0333102415610874
DO - 10.1177/0333102415610874
M3 - Journal article
C2 - 26502740
SN - 0333-1024
VL - 36
SP - 624
EP - 639
JO - Cephalalgia : an international journal of headache
JF - Cephalalgia : an international journal of headache
IS - 7
ER -