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. 2014 Jul 4;13(3):154-9.

Effect of NOS3 Gene Polymorphism on Response to Tricyclic Antidepressants in Migraine Attacks

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Free PMC article

Effect of NOS3 Gene Polymorphism on Response to Tricyclic Antidepressants in Migraine Attacks

Aliasghar Molana et al. Iran J Neurol. .
Free PMC article

Abstract

Background: Migraine is a chronic neurological disorder, characterized by recurrent moderate to severe headaches. Worldwide migraine affects 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 effects 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 1(st) 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 3(rd) 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.

Keywords: Headache; Migraine; Nitric Oxide Synthase 3; Polymorphism; Tricyclic Antidepressants.

Figures

Figure 1
Figure 1
Patients’ genotype determination by use of Sanger sequencing by considering location of the SNP in NOS3: (A) Single black peak indicate homozygote in the form of GG genotype. (B) Single red peak indicate homozygote in the form of TT genotype. (C) Double peak (red and black) indicate heterozygote in the form of GT genotype
Figure 2
Figure 2
Comparison of the genotypes according to mRNA expression
Figure 3
Figure 3
Comparison of the genotypes according to the mean nitric oxide level before and after  use of tricyclic antidepressants
Figure 4
Figure 4
Comparison of the genotypes according to the mean intensity of headaches before and after use of tricyclic antidepressants. Verbal Numerical Rating Scale* (VNRS*): 0 → no pain;  1-3 → mild pain; 4-6 → moderate pain; 7-10 → severe pain
Figure 5
Figure 5
Comparison of the genotypes according to mean frequency of migraine attacks  before and after use of tricyclic antidepressants

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References

    1. Ruiz de Velasco I, Gonzalez N, Etxeberria Y, Garcia-Monco JC. Quality of life in migraine patients: a qualitative study. Cephalalgia. 2003;23(9):892–900. - PubMed
    1. The International Classification of Headache Disorders: 2nd edition. Cephalalgia . 2004;24(Suppl 1):9–160. - PubMed
    1. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2163–96. - PMC - PubMed
    1. Bartleson JD, Cutrer FM. Migraine update. Diagnosis and treatment. Minn Med. 2010;93(5):36–41. - PubMed
    1. Edvinsson L, Ekman R, Jansen I, McCulloch J, Uddman R. Calcitonin gene-related peptide and cerebral blood vessels: distribution and vasomotor effects. J Cereb Blood Flow Metab. 1987;7(6):720–8. - PubMed

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