Tehran University of Medical Sciences Iranian Journal of Public Health 2251-6085 45 12 2016 12 27 1625 1635 Elahe MOZAFFARI Biotechnology Research Center, Islamic Azad University, Shahrekord Branch, Shahrekord, Iran Abbas DOOSTI Biotechnology Research Center, Islamic Azad University, Shahrekord Branch, Shahrekord, Iran Asghar ARSHI Young Researchers and Elite Club, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran Mostafa FAGHANI Dept. of Animal Sciences, Faculty of Agriculture, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran 2016 12 27 2016 12 27 Background: Migraine is a common debilitating primary headache disorder with current head pain attacks, which contributes to physical activity dysfunctions in chronic pain phase. PGE2 and PGI2 are two important prostaglandins synthesised by COX-2 enzymes, involved in migraine pain signals. COX-2 modulation is essential in treatment and pathogenesis of migraine. This study aimed to investigating the association between COX-2 gene polymorphisms with the risk of migraine susceptibility in migraine patients with related and unrelated parents. Methods: This case- control study was based on 100 migraine patients and 100 non-migraine subjects in Bushehr province, Iran in 2013. Genomic DNA of blood samples was extracted and genotyping of COX-2-765G>C (rs20417) and COX-2-1195A>G (rs689466) gene variants was investigated by PCR-RFLP method. Statistical analyses were accomplished using the SPSS software package. Results: There was a significant differences in the frequencies of the COX-2-765G>C and COX-2-1195A>G genotypes between migraine patients and controls (P≤0.05). Conclusion: COX-2-765CC, COX-2-765CG, COX-2-1195GG and COX-2-1195AG genotypes can increase the risk of migraine significantly. As the first study in Iran, we are hopeful to achieve greater results about the relevancy of COX-2 gene, migraine and pain signals pathway by repeating these experiments on more samples.   https://ijph.tums.ac.ir/index.php/ijph/article/view/8638 https://ijph.tums.ac.ir/index.php/ijph/article/download/8638/5481