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.
Lemos
Carolina
C
Department Estudos de Populações, ICBAS, Universidade do Porto, Centro Hospitalar do Porto-Hospital de Santo António, Portugal. absousa@icbas.up.pt
Mendonça
Denisa
D
Pereira-Monteiro
José
J
Barros
José
J
Sequeiros
Jorge
J
Alonso
Isabel
I
Sousa
Alda
A
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