The Association of A1438G Single Nucleotide Polymorphism in the 5-HT2A Receptor Gene with the Risk of Migraine Disease

Document Type : Original Article(s)

Authors

1 Department of Biology, School of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran

2 Assistant Professor, Department of Biology, School of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran

3 Assistant Professor, Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Migraine is a common neurodegenerative disorder, and the loss of the function of several genes in the serotonergic system is involved in the susceptibility to this disease. In this study, the association of the functional polymorphism of A1438G single nucleotide in the promoter of the 5-HT2A receptor gene with migraine susceptibility was studied.Methods: Genomic DNA was extracted from blood samples of 109 patients with migraine and 107 healthy individuals. Then, the fragment of the promoter of the HTR2A gene, which contained A1438G polymorphism, was amplified using polymerase chain reaction (PCR) technique. To determine the genotype of each individual, the product of polymerase chain reaction was digested with MspI enzyme.Findings: Genotype AA increased the risk of migraine disease by two folds (P = 0.03). Moreover, allele A increased the risk of migraine significantly (P = 0.01).Conclusion: Based on the results of this study, it is suggested that the genotype AA in the A1438G single nucleotide of the HTR2A receptor gene can increase the risk of migraine disease, which may be due to the effect of allele A on enhancement of promoter activity, receptor expression, and consequently, the effect of it on the contraction of the vessels that is present in migraine headaches.

Keywords

References

  1. Wober-Bingol C. Epidemiology of migraine and headache in children and adolescents. Curr Pain Headache Rep 2013; 17(6): 341.
  2. Olesen J. The international classification of headache disorders. 2nd edition (ICHD-II). Rev Neurol (Paris) 2005; 161(6-7): 689-91.
  3. Zarshenas MM, Petramfar P, Firoozabadi A, Moein MR, Mohagheghzadeh A. Types of headache and those remedies in traditional persian medicine. Pharmacogn Rev 2013; 7(13): 17-26.
  4. Kaniecki RG. Basilar-type migraine. Curr Pain Headache Rep 2009; 13(3): 217-20.
  5. Robbins MS, Lipton RB. The epidemiology of primary headache disorders. Semin Neurol 2010; 30(2): 107-19.
  6. Stovner LJ, Zwart JA, Hagen K, Terwindt GM, Pascual J. Epidemiology of headache in Europe. Eur J Neurol 2006; 13(4): 333-45.
  7. Lay CL, Broner SW. Migraine in women. Neurol Clin 2009; 27(2): 503-11.
  8. Hashemilar M, Aminisani N, Savadi Oskoui D, Yosefian M. The Prevalence of migraine among student of Ardabil University of Medical Sciences, 2003. J Ardabil Univ Med Sci 2004; 4(1): 64-9. [In Persian].
  9. Ghayeghran A, Fathe Sami S. Survey on prevalence of migraine in highschool students of Rasht City. J Guilan Univ Med Sci 2004; 13(50): 22-6. [In Persian].
  10. Ayatollahi SM, Khosravi A. Prevalence of migraine and tension-type headache in primary-school children in Shiraz. East Mediterr Health J 2006; 12(6): 809-17.
  11. Haut SR, Bigal ME, Lipton RB. Chronic disorders with episodic manifestations: focus on epilepsy and migraine. Lancet Neurol 2006; 5(2): 148-57.
  12. Russell MB, Ducros A. Sporadic and familial hemiplegic migraine: pathophysiological mechanisms, clinical characteristics, diagnosis, and management. Lancet Neurol 2011; 10(5): 457-70.
  13. Schurks M. Genetics of migraine in the age of genome-wide association studies. J Headache Pain 2012; 13(1): 1-9.
  14. Spierings EL. Pathogenesis of the migraine attack. Clin J Pain 2003; 19(4): 255-62.
  15. Naito Y, Ishii M, Nagamine A, Imagawa A, Shida K, Takahashi J, et al. Association of the A-1438G polymorphism in serotonin 2A receptor in migraine with aura among Japanese patients. Biol Pharm Bull 2010; 33(10): 1751-3.
  16. Hamel E. Serotonin and migraine: Biology and clinical implications. Cephalalgia 2007; 27(11): 1293-300.
  17. Cook EH, Jr., Fletcher KE, Wainwright M, Marks N, Yan SY, Leventhal BL. Primary structure of the human platelet serotonin 5-HT2A receptor: Identify with frontal cortex serotonin 5-HT2A receptor. J Neurochem 1994; 63(2): 465-9.
  18. Parsons MJ, D'Souza UM, Arranz MJ, Kerwin RW, Makoff AJ. The -1438A/G polymorphism in the 5-hydroxytryptamine type 2A receptor gene affects promoter activity. Biol Psychiatry 2004; 56(6): 406-10.
  19. Turecki G, Briere R, Dewar K, Antonetti T, Lesage AD, Seguin M, et al. Prediction of level of serotonin 2A receptor binding by serotonin receptor 2A genetic variation in postmortem brain samples from subjects who did or did not commit suicide. Am J Psychiatry 1999; 156(9): 1456-8.
  20. Peng JM, Yu YJ, Su LD, Luo X. Meta-analysis of 5-hydroxytryptamine type 2A receptor polymorphisms and migraine susceptibility. Int J Neurosci 2014; 124(12): 882-9.
  21. Ollat H. Serotonin agonists and antagonists in migraine. Pathol Biol (Paris) 1992; 40(4): 389-96. [In French].
  22. Yucel Y, Coskun S, Cengiz B, Ozdemir HH, Uzar E, Cim A, et al. Association of polymorphisms within the serotonin receptor genes 5-HTR1A, 5-HTR1B, 5-HTR2A and 5-HTR2C and migraine susceptibility in a Turkish population. Clin Psychopharmacol Neurosci 2016; 14(3): 250-5.
  23. Erdal ME, Yilmaz M, Herken H, Kocoglu H, Bayazit YA. The 1438G/A polymorphism of the 5-HT2A receptor gene is associated with aura in migraine. The Pain Clinic 2003; 15(3): 315-9.
  24. Hoyer D, Hannon JP, Martin GR. Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav 2002; 71(4): 533-54.
  25. Moses EL, Drevets WC, Smith G, Mathis CA, Kalro BN, Butters MA, et al. Effects of estradiol and progesterone administration on human serotonin 2A receptor binding: A PET study. Biol Psychiatry 2000; 48(8): 854-60.
Journal of Isfahan Medical School
Volume 36, Issue 476 - Serial Number 476
March and April 2018
Pages 386-391

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History

  • Receive Date: 04 December 2017
  • Revise Date:
  • Accept Date: 06 April 2022

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