Variations in the cannabinoid receptor 1 gene predispose to migraine.
In animal models endogenous cannabinoids have an inhibitory effect on trigeminovascular activation through the cannabinoid receptor 1 (CB1), although there is no evidence of the potential role of CB1 in human migraine. In this study we applied single marker association and haplotypic trend regression analysis to investigate the relationship between the CB1 gene (CNR1) and headache with migraine symptoms (nausea, photophobia and disability, measured by the ID-migraine questionnaire). We identified our controls (CO=684) as those who have not reported ID-migraine symptoms at all and defined migraine headache sufferers (M=195) as those who reported all three symptoms. The CNR1 was covered by 10 SNPs located throughout the gene based on haplotype tagging (htSNP) and previous literature. Our results demonstrated a significant haplotypic effect of CNR1 on migraine headaches (p=0.008, after permutation p=0.017). This effect was independent of reported depression or drug/alcohol abuse although using neuroticism in the analysis as covariant slightly decreased this association (p=0.027, permutated p=0.052). These results suggest a significant effect of CNR1 on migraine headaches that might be related to the alteration of peripheral trigeminovascular activation. In addition, this is the first study to demonstrate the effectiveness of using trait components combinations to define extreme phenotypes with haplotype analysis in genetic association studies for migraine. However, further studies are needed to elucidate the role of CNR1 and the cannabinoid system in migraine.
Juhasz
Gabriella
G
Neuroscience and Psychiatry Unit, University of Manchester, Manchester, UK. gabriella.juhasz@manchester.ac.uk
Lazary
Judit
J
Chase
Diana
D
Pegg
Emma
E
Downey
Darragh
D
Toth
Zoltan G
ZG
Stones
Kathryn
K
Platt
Hazel
H
Mekli
Krisztina
K
Payton
Antony
A
Anderson
Ian M
IM
Deakin
J F William
JF
Bagdy
Gyorgy
G
D000293:Adolescent; D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*; D012044:Regression Analysis; D012737:Sex Factors; D011795:Surveys and Questionnaires; D044465:White People; D055815:Young Adult
D043884:Receptor, Cannabinoid, CB1