BDNF and CGRP interaction: implications in migraine susceptibility.
OBJECTIVE
Migraine pathophysiology involves several pathways. Our aims were to explore a possible role of the brain-derived neurotrophic factor gene (BDNF) in migraine susceptibility; to study, for the first time, the calcitonin gene-related peptide gene (CGRP); and a possible interaction between the two.


METHODS
Using a case-control approach, four tagging single nucleotide polymorphisms (SNPs) (rs7124442, rs6265, rs11030107, and rs2049046) of BDNF and one tagging SNP-rs1553005-of CGRP were analyzed in 188 cases and 287 controls. A multivariable logistic regression was performed, adjusting for gender. Allelic and haplotypic frequencies were estimated. Interaction was assessed by a stepwise multivariable-logistic regression and confirmed by a multifactor dimensionality reduction analysis.


RESULTS
No significant main effects were found; however, a significant interaction was found between BDNF and CGRP, showing an increased risk for the AT-genotype of rs2049046 and the GC-genotype of rs1553005 (odds ratio=1.88, 95% confidence interval: 1.20-2.93) for migraineurs.


CONCLUSIONS
Our data support the hypothesis of an interaction between BDNF and CGRP in migraine susceptibility that should be further explored.
Department Estudos de Populações, ICBAS, Universidade do Porto, Centro Hospitalar do Porto-Hospital de Santo António, Portugal. absousa@icbas.up.pt
Carolina
C
Lemos
Denisa
D
Mendonça
José
J
Pereira-Monteiro
José
J
Barros
Jorge
J
Sequeiros
Isabel
I
Alonso
Alda
A
Sousa
D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics*; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000235:genetics*; D058011:Multifactor Dimensionality Reduction; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019208:Brain-Derived Neurotrophic Factor; D015740:Calcitonin Gene-Related Peptide