MTHFR Gene polymorphisms and susceptibility to Migraine Attacks

Background: Migraine consisting of migraine with aura (MA) and migraine without aura (MO) is a painful neurovascular disorder affecting approximately 16% of the general population. A combination of genetic and environmental factors is involved in the pathogenesis of migraine. The MTHFR enzyme is involved in homocysteine (Hcy) metabolism and it has been reported that 1298 A to C and 677 C to T mutations in the MTHFR gene are associated with an increased in plasma Hcy levels. Hcy is a highly reactive amino acid and causes endothelial injury. Because a plausible theory about vascular impairment in migraine, it is considered that mutations in MTHFR gene and folate metabolism are associated with migraine. Materials and Methods: In total, 75 patients with migraine (24 with MA and 51with MO) in accordance with the IHS criteria participated in this case-control study. Control group were 128 normal matched healthy subjecys who selected from same region without history of migraine or other neurologic disorder after interviewing and examining by a physician. Mean age at entry was 36.42±9.6 and 31.64±8.9 years old in migraine and control group respectively. MTHFR polymorphisms were investigated by PCR-RFLP. Results: Genotypic results indicated that the prevalence of the MTHFR 677TT genotype in migraine subjects was higher than control (17.3% and 3.1% respectively, P<0.001). Interestingly the risk of migraine was 6-fold higher in subjects possessing the MTHFR 677T homozygous variant (OR=6.5; CI95%: 2.03-20.76). No significant difference in the prevalence of MTHFR A1298C genotypes was observed in migraine group when compared to controls (P>0.001). Conclusion: It seems that MTHFR C677T is a potential genetic risk factor for migraine attacks, both in MA and MO subclasses in Iranian population. C677T and A1298C joint effect could amplify the potential influence of each SNPs.