title: Investigation of polymorphisms in genes involved in estrogen metabolism in menstrual migraine.
abstract: Migraine is a common, disabling headache disorder, which is influenced by multiple genes and environmental triggers. After puberty, the prevalence of migraine in women is three times higher than in men and >50% of females suffering from migraine report a menstrual association, suggesting hormonal fluctuations can influence the risk of migraine attacks. It has been hypothesized that the drop in estrogen during menses is an important trigger for menstrual migraine. Catechol-O-methyltransferase (COMT) and Cytochrome P450 (CYP) enzymes are involved in estrogen synthesis and metabolism. Functional polymorphisms in these genes can influence estrogen levels and therefore may be associated with risk of menstrual migraine. In this study we investigated four single nucleotide polymorphisms in three genes involved in estrogen metabolism that have been reported to impact enzyme levels or function, in a specific menstrual migraine cohort. 268 menstrual migraine cases and 142 controls were genotyped for rs4680 in COMT (Val158Met), rs4646903 and rs1048943 in CYP1A1 (T3801C and Ile462Val) and rs700519 in CYP19A1 (Cys264Arg). Neither genotype nor allele frequencies for the COMT and CYP SNPs genotyped were found to be significantly different between menstrual migraineurs and controls by chi-square analysis (P>0.05). Therefore we did not find association of functional polymorphisms in the estrogen metabolism genes COMT, CYP1A1 or CYP19A1 with menstrual migraine. Further studies are required to assess whether menstrual migraine is genetically distinct from the common migraine subtypes and identify genes that influence risk.
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
authors.forename: Heidi G
authors.initials: HG
authors.lastname: Sutherland
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
authors.forename: Morgane
authors.initials: M
authors.lastname: Champion
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
authors.forename: Amelie
authors.initials: A
authors.lastname: Plays
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
authors.forename: Shani
authors.initials: S
authors.lastname: Stuart
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
authors.forename: Larisa M
authors.initials: LM
authors.lastname: Haupt
authors.affiliation: Clinithink Limited, Bridgend, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Frith
authors.affiliation: Centre for Neuroscience & Trauma, Blizard Institute of Cell and Molecular Science, London, UK.
authors.forename: E Anne
authors.initials: EA
authors.lastname: MacGregor
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia. Electronic address: lyn.griffiths@qut.edu.au.
authors.forename: Lyn R
authors.initials: LR
authors.lastname: Griffiths
mesh_terms: D000328:Adult; D001141:Aromatase / Q000235:genetics*; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004967:Estrogens / Q000235:genetics / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008597:Menstrual Cycle / Q000235:genetics*; D008598:Menstruation / Q000235:genetics*; D008875:Middle Aged; D008881:Migraine Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D006113:United Kingdom; D055815:Young Adult
chemical_list: D004967:Estrogens; D001141:Aromatase; C561410:CYP19A1 protein, human; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: COMT; CYP genes; Estrogen metabolism; Menstrual migraine; Migraine; Single nucleotide polymorphism