Interacting Determinants of Migraine Susceptibility

Rod Lea1, Lyn Griffiths2, Genomics Research Centre, Griffith University;, Genomics Research Centre, Griffith University

Migraine is a debilitating neurovascular disorder that affects at least 12% of the Caucasian population. The aetiology of migraine is likely to be comprised of a number of susceptibility genes acting synergistically to confer a moderate effect on the disease. Genes able to affect vascular endothelial function represent plausible candidates given the marked cerebral blood flow changes that occur in migraineurs. The objectives of our study were to investigate the MTHFR (C667T) and ACE (I/D) functional gene variants for involvement in migraine susceptibility and particularly, to test for potential interactions between these variants in relation to migraine risk. For this study we utilised a balanced, matched case-control association design, with groups consisting of 270 patients diagnosed with migraine with aura (MA) and without aura (MO) and 270 unaffected controls. Multiple logistic regression (LR) analysis was performed incorporating data for both the MTHFR C677T mutation and the ACE ID polymorphism. The main effects analysis indicated that the MTHFR TT genotype substantially increased risk of disease after adjusting for the effect of the ACE D alleles (OR = 2.405, 95% CI:1.296 – 4.464, P = 0.005). Interestingly, entering the interaction term “ACE´MTHFR” provided good evidence that the MTHFR (TT) and ACE (ID/DD) genotypes act synergistically to further increase migraine susceptibility (OR = 2.893, 95% CI:1.464 - 5.716, P = 0.002). We are currently attempting to substantiate these positive findings in an independent sample of affected pedigrees but the present results provide good stand-alone evidence for genetic interaction underlying migraine susceptibility.