Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphism (677CT) and Increased Susceptibility to Migraine in Egyptian Population: A Case-Control Study

Abstract
Background: Migraine is a recurrent neurovascular disor-der which lowers the quality of life. Middle-aged women are more susceptible to migraine than men. It is either migraine with aura (MA) or migraine without aura (MO). Molecular genetic studies of migraine have investigated many polymor-phisms possibly associated with migraine particularly rs4846049 and A1298C polymorphisms. Methylenetetrahy-drofolate Reductase (MTHFR) gene 677CT polymorphism is one of the proposed genetic changes affecting migraine.
Aim of Study: This study aimed at assessing its role in migraine in Egyptian population and its relation to the clinical manifestations of the disease and to find a possible link to effectiveness or resistance to 677CT treatment protocols.
Subjects and Methods: This study was conducted on (180) subjects who were divided into two groups: Group I (patients, group) which included (120) adult patients with migraine recruited from Headache Clinic in Ain Shams University Hospitals and were diagnosed with migraine according to ICHD diagnostic criteria 3rd edition beta version (2013), and Group II (control group) which included (60) age-and sex-matched apparently healthy subjects. MTHFR 677CT poly-morphism was assessed using Restriction Fragment Length Polymerase Chain Reaction (RFLP-PCR) technique.
Results: The study demonstrated a significant association between MTHFR gene polymorphism (C677T) and migraine (p<0.001), Odd's Ratio (OR)=6.0, 95% CI (1.84-19.59). Both heterozygous (CT) and homozygous (TT) female patients were significantly more susceptible to develop migraine than both heterozygous (CT) and homozygous (TT) males (x2: 12.48, p<0.05). Patients with homozygous type (TT) showed positive significant risk to develop aura (50%) (p<0.001), OR=45.0, 95%CI (5.26-385.19) while patients with hetero-zygous type (CT) showed positive significant risk to have attacks of migraine associated with photophobia (58.3%) (p<0.001), OR=21.0, 95%CI (3.10-142.21) or phonophobia (56.5%) (p<0.001), OR=13.0, 95%CI (2.09-81.05) or both. Significant statistical difference was seen on comparing between MTHFR gene polymorphism (677CT) and attack severity (x2: 8.57, p<0.05), while no significant difference was seen between gene polymorphism and analgesic treatment dose (x2: 1.86, p>0.05).
Conclusion: The study demonstrates a significant associ-ation between MTHFR gene polymorphism (677CT) and occurrence of migraine and its preceding and accompanying clinical manifestations in Egyptian population, attack severity and increased risk of disease occurrence. Unfortunately, MTHFR gene polymorphism (677CT) showed no statistical association with analgesic treatment dose.