Toll Like Receptor-4 896A/G Gene Variation, a Risk Factor for Migraine Headaches

Background: The pathogenesis of migraine involves immune-mediated mechanisms in the vascular endothelium. Toll like receptor 4 (TLR-4) is a signaling receptor of innate immunity which plays a role in various neuropathologies related to neuron inflammation. Objective: This case/control study is aimed to investigate whether TLR- 4 896A/G variation is related to migraine headaches in an Iranian population. Methods: A total of 170 migraine patients (130 females, mean age 33.24 ± 11 years) and 170 age, sex, and ethnicity matched healthy controls (118 females, mean age of 31 ± 10 years) were recruited. Genotyping was carried out using the tetra primer amplification refractory mutation system (ARMS)-PCR. Results: The frequency of G allele was higher in migraine patients than the controls (15% vs. 4.7%; p<0.0001). Interestingly, the distribution of heterozygous 896A/G genotype statistically differed between migraineurs and controls (25.3% vs. 8.2%, p=0.00002, or 3.87, 95% CI; 2.02-7.4). Multivariate logistic regression analysis indicated that G allele in affected female migraineurs is an independent factor associated with increased risk of migraine (OR 3.2, 95% CI 1.23-8.24, p=0.01). Conclusion: Our results showed TLR-4 polymorphism as a genetic risk factor for migraine. However, further studies in different populations are required to elucidate the precise role of TLR-4 896A/G mutation in susceptibility to migraine.