Toll like receptor-4 896A/G gene variation, a risk factor for migraine headaches

Iran J Immunol. 2012 Sep;9(3):159-67.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Gene Frequency
  • Gene-Environment Interaction
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Immunity, Innate
  • Inflammation Mediators / metabolism
  • Iran
  • Male
  • Migraine Disorders / genetics*
  • Migraine Disorders / immunology
  • Neurogenic Inflammation / genetics
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Sex Factors
  • Toll-Like Receptor 4 / genetics*
  • Trigeminal Nerve / immunology*
  • Young Adult


  • Inflammation Mediators
  • Toll-Like Receptor 4