title: Genetic variants of angiotensin converting enzyme and methylenetetrahydrofolate reductase may act in combination to increase migraine susceptibility.
abstract: Migraine, with and without aura (MA and MO), is a prevalent and complex neurovascular disorder that is likely to be influenced by multiple genes some of which may be capable of causing vascular changes leading to disease onset. This study was conducted to determine whether the ACE I/D gene variant is involved in migraine risk and whether this variant might act in combination with the previously implicated MTHFR C677T genetic variant in 270 migraine cases and 270 matched controls. Statistical analysis of the ACE I/D variant indicated no significant difference in allele or genotype frequencies (P > 0.05). However, grouping of genotypes showed a modest, yet significant, over-representation of the DD/ID genotype in the migraine group (88%) compared to controls (81%) (OR of 1.64, 95% CI: 1.00-2.69, P = 0.048). Multivariate analysis, including genotype data for the MTHFR C677T, provided evidence that the MTHFR (TT) and ACE (ID/DD) genotypes act in combination to increase migraine susceptibility (OR = 2.18, 95% CI: 1.15-4.16, P = 0.018). This effect was greatest for the MA subtype where the genotype combination corresponded to an OR of 2.89 (95% CI:1.47-5.72, P = 0.002). In Caucasians, the ACE D allele confers a weak independent risk to migraine susceptibility and also appears to act in combination with the C677T variant in the MTHFR gene to confer a stronger influence on the disease.
authors.affiliation: Genomic Research Centre, School of Health Science, Griffith University, Parklands Drive, Southport, QLD 4217, Australia.
authors.forename: Rod A
authors.initials: RA
authors.lastname: Lea
authors.forename: Micky
authors.initials: M
authors.lastname: Ovcaric
authors.forename: James
authors.initials: J
authors.lastname: Sundholm
authors.forename: Leah
authors.initials: L
authors.lastname: Solyom
authors.forename: John
authors.initials: J
authors.lastname: Macmillan
authors.forename: Lyn R
authors.initials: LR
authors.lastname: Griffiths
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016001:Confidence Intervals; D004198:Disease Susceptibility; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D008881:Migraine Disorders / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D012306:Risk
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2); D007703:Peptidyl-Dipeptidase A