Tehran University of Medical Sciences Current Journal of Neurology 2717-011X 13 3 2014 09 15 154 159 Aliasghar Molana Department of Neuroscience, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. Masoud Mehrpour Department of Neurology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran. Nasim Vousooghi Department of Neuroscience, School of Advanced Technologies in Medicine AND Genetics Laboratory, Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran. Mahmoud Reza Hajighasem Department of Neuroscience, School of Advanced Technologies in Medicine AND Brain and Spinal Cord Injury Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran. Mohammad Taghi Joghataei Department of Neuroscience, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. 2015 10 14 Background: Migraine is a chronic  neurological  disorder, characterized  by recurrent  moderate to severe headaches. Worldwide migraine a=ects nearly 15%. Studies suggest that genes involved in the production of nitric oxide (NO) may act as genetic  factors for migraine. NO synthase  3 (NOS3) by expressing  enzyme NOS regulates  endothelial  derived NO. One  class of  medications   used  as  first-line treatment in migraine prophylaxis is tricyclic antidepressants (TCAs). The aim of this study  was to determine  e=ects  of NOS3 gene Glu298Asp polymorphism  in  the  production  of  NO and response of patients to TCAs in migraine attacks. Methods: A total of 80 migraine patients  were invited to participate   in  the  study.  Patients  recorded   the characteristics of their migraine attacks such as frequency of attacks and intensity of headaches for the 1st  month  of the study. Then peripheral blood samples were taken from all subjects in order to determine patients’ genotype distribution,  mRNA  expression  level  of  NOS3 and   NO content  of plasma. Patients were then instructed  to use 25 mg nortriptyline at night before bed for 3 months. At the end of 3rd  month of the treatment patients  again recorded the  migraine characteristics  for  1  month   and   blood sampling was performed  in order to determine the level of plasma NO. Results: The patients’ genotype distribution  for TT,  GT, and GG was 9, 24, and 47 subjects, respectively. Mean NO level in patients  with TT genotype was less in comparison to GT and GG genotypes before and after use of TCAs (P < 0.05). Mean  intensity  of headaches in patients  with  TT genotype  was  lower  in  comparison   to   GT   and   GG genotypes before and after use of TCAs (based on verbal numerical   rating   scale).  Mean  frequency   of  migraine attacks after use of TCAs was significantly decreased in all genotypes of NOS3 Glu298Asp polymorphism particularly in TT genotype (P < 0.05). Conclusion: Presence of T allele of the Glu298Asp polymorphism may be a factor for TT genotype patients to produce less NO and is a favorable factor for better response to TCAs in reducing  migraine  attacks in comparison to GT and GG genotypes. https://ijnl.tums.ac.ir/index.php/ijnl/article/view/603 https://ijnl.tums.ac.ir/index.php/ijnl/article/download/603/199