Influence of TNF-α and ESR1 polymorphisms on vascular, hormonal and inflammatory biomarkers in migraine

Background and Objective: Migraine is a highly prevalent multifactorial and polygenic neurological disorder associated with genetic, environmental and hormonal changes. Methylenetetrahydrofolatereductase (MTHFR), tumor necrosis factor (TNF-α), estrogen and genetics have been reported to play significant roles in migraine. The purpose of this study was to determine the impact of TNF-α and ESR genetic polymorphisms on migraine development. Materials and Methods: Female patients diagnosed with migraine (n = 129) and healthy controls (n = 100) were recruited for the study. Plasma concentrations of vitamin B6 and TNF-α were measured using enzyme linked immunosorbent assay kits. Vitamins B9 and B12 were measured using a competitive immunoassay based on a direct chemi-luminescent technology while genotyping was performed using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique. Results: The G-allele of ESR1 325C>G (OR = 2.61, p = 0.001), A allele of ESR1 594G>A (OR = 2.99, p<0.001) and A-allele of TNF-α-308G>A (OR = 9.47, p<0.001) were significantly associated with migraine among female Malays. However, the T-allele of MTHFR 677C>T was not associated with migraine. Vitamin B6 (10.9 vs 20.3 ng mLG-1) was significantly (p<0.001) lower and TNF-α (16.8 vs 2.9 pg mLG-1) was significantly (p<0.001) higher among migraine patients compared to healthy subjects. In addition, vitamin B6 level was significantly lower among migraine patients having the MTHFR 677C>T (8.6 vs 16.7 ng mLG-1, p = 0.008) and TNF-α-308G>A (9.6 vs 21.9 pg mLG-1, p<0.001) compared to the healthy subjects. Similarly, the TNF-α levels were significantly higher (44.7 vs 15.7 pg mLG-1, p = 0.013) among migraine patients with TNF-α-308G>A polymorphisms compared to the healthy subjects. The variant allele of TNF-α-308G>A, ESR1 325C>G and ESR1 594 G>A significantly predisposed patients to higher risk for migraine, but not the MTHFR 677C>T variant allele. Conclusion: Serum levels of TNF-α and vitamin B6 were associated with TNF-α-308G>A polymorphism among Malay or female subjects.