Tugce KAYMAZ, Ebru ÖNALAN, İlay BURAN KAVURAN, Ayşe BERİLGEN GÜRGÖZE, Bülent MÜNGEN

Miyelin Oligodendrosit Glikoprotein (MOG) Gen Polimorfizminin, (Val142Leu) Migrene Genetik Duyarlılık ile Doğrudan Bir İlişkisi Yoktur

Amaç: İmmün yanıtta yer alan genler, migrende olası aday genleri gösterir. Bu genlerden biri, kompleman kaskadına aracılık etmede önemli bir rol oynayan miyelin oligodendrosit glikoprotein genidir (MOG). Çalışmamızın amacı; migren atak sıklığında MOG G511C (Val142Leu; rs2857766) polimorfizminin etkisini göstermektir. Yöntem: 101 Türk migren hastası kohortunda ve 101 sağlıklı denekten oluşan kontrol grubunda MOG Val142Leu alellerinin dağılımı incelendi. Bu polimorfizmi genotiplemek için restriksiyon fragman uzunluk polimorfizmi (RFLP) yapıldı. Bulgular: MOG Leu allel frekansının, migren hastalarında yetersiz temsil edildiğinin belirlenmesine rağmen hasta ve kontrol grubu genotipleri ve allel frekansları arasında anlamlı bir farklılık elde edilemedi [OR=0.47 (0.21-1.08), genotipler için p=0.053; OR=0.50 (0.23-1.11), aleller için p=0.060]. Ancak MOG G511C (Val142Leu) polimorfizmi ile azalmış migren atak sıklığı arasında istatistiksel olarak anlamlı bir ilişki saptandı [OR=11.71 (1.32-103.77), p=0.013]. Ayda iki veya daha az atak geçiren migren hastalarında Val/Leu genotip sıklığı artmıştır. Sonuç: Migren atak sıklığı, MOG Val142Leu heterozigot genotipi ile ilişkili olabilir. Dolayısıyla MOG geminin, insan lökosit antijeni (HLA) bölgesinde migrene genetik yatkınlıkla ilişkili olabileceğini öngörmekteyiz.

Anahtar Kelimeler:

Migren, miyelin oligodendrosit glikoprotein, polimorfizm, HLA, Val142Leu

No Direct Association of Myelin Oligodendrocyte Glycoprotein (MOG) Gene Polymorphism (Val142leu) in Genetic Susceptibility to Migraine

Objective: Genes which are involved in immune response portray possible candidate genes in migraine. One of those genes is that myelin oligodendrocyte glycoprotein (MOG) that plays an important role in mediating the complement cascade. The purpose of our study is to show the effect of MOG G511C (Val142Leu; rs2857766) polymorphism in migraine attack frequency. Materials and Methods: In the cohort of 101 Turkish migraine patients and in a control group of 101 healthy subjects, MOG Val142Leu alleles’ distribution was examined. Restriction fragment length polymorphism (RFLP) was carried out to genotype this polymorphism. Results: Although MOG Leu allele frequency was determined as under-represented in migraine patients, any significant difference between the patient and control groups’ genotype, and allele frequencies were not obtained [OR=0.47 (0.21-1.08), p=0.053 for genotypes; OR=0.50 (0.23-1.11), p=0.060 for alleles]. However, a statistically significant relationship between MOG G511C (Val142Leu) polymorphism and the decreased migraine attack frequency was determined [OR=11.71 (1.32-103.77), p=0.013]. Val/Leu genotype frequency increrased in migraine patients with two or fewer attacks per month. Conclusion: Migraine attack frequency might be related with MOG Val142Leu heterozygote genotype. So we think that MOG gene might be related to genetic susceptibility to migraine in the human leukocyte antigen (HLA) region.

Keywords:

Migraine, Myelin oligodendrocyte glycoprotein, Polymorphism, HLA, Val142Leu,

PDF

___

1. De Boer I, van den Maagdenberg AM, Terwindt GM. Advance in genetics of migraine. Curr Opin Neurol 2019;32(3):413-21.
2. Stovner L, Hagen K, Jensen R, et al. The global burden of headache: adocumentation of headache prevalence and disability worldwide. Cephalalgia 2007;27:193-210.
3. Harriott AM, Takizawa T, Chung DY, Chen SP. Spreading depression as a preclinical model of migraine. J Headache Pain 2019;20(1):45.
4. Gormley P, Anttila V, Winsvold BS, et al. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. Nat Genet 2016;48(8):856-66.
5. Davey G, Sedgwick P, Maier W, Visick G, Strachan DP, Anderson HR. Association between migraine and asthma: Matched case-control study. Br J Gen Pract 2002;52:723-7.
6. Giacovazzo M, Valeri M, Piazza A, et al. Elevated frequency of HLA shared-haplotypes in migraine families. Headache 1987;27:575-7.
7. Rainero I, Grimaldi LM, Salani G, et al. Association between the tumor necrosis factor-alpha-308 G/A gene polymorphism and migraine. Neurology 2004;62:141-3.
8. Trabace S, Brioli G, Lulli P, et al. Tumor necrosis factor gene polymorphism in migraine. Headache 2002;42: 341-5.
9. Rainero I, Dall’Omo AM, Rubino E, et al. HLA-DRB1 genotyping in Italian migraine patients. Neurosci Lett 2006;393:90-3.
10. Amadou C, Ribouchon MT, Mattei MG, et al. Localization of new genes and markers to the distal part of the human major histocompatibility complex (MHC) region and comparison with the mouse: new insights into the evolution of mammalian genomes. Genomics 1995;26:9-20.
11. Gardinier MV, Amiguet P, Linington C, Matthieu JM. Myelin oligodendrocyte glycoprotein is a unique member of the immunoglobulin superfamily. J Neurosci Res 1992;33:177-87.
12. Johns TG, Bernard CC. The structure and function of myelin oligodendrocyte glycoprotein. J Neurochem 1999;72:1-9.
13. Ferrari MD. Migraine. Lancet 1998;351:1043-51.
14. Olesen J. The international classification of headache disorders. International Headache Society 2004;24 (1):24-36.
15. Gomez-Lira M, Moretto G, Bonamini D, et al. Myelin oligodendrocyte glycoprotein polymorphisms and multiple sclerosis. J Neuroimmunol 2002;133(1-2):241-3.
16. Alfonso SD, Bolognesi E, Guerini FR, et al. A sequence variation in the MOG gene is involved in multiple sclerosis susceptibility in Italy. Genes Immun 2008;9:7-15.
17. Sacco S, Ricci S, Degan D, Carolei A. Migraine in women: The role of hormones and their impact on vascular diseases. J Headache Pain 2012;13:177-89.
18. Zhang Z, Cerghet M, Mullins C, Williamson M, Bessert D, Skoff R. Comparison of in vivo and in vitro subcellular localization of estrogen receptors alpha and beta in oligodendrocytes. J Neurochem 2004;89(3):674-84.
19. Zai G, King N, Wigg K, et al. Genetic study of the myelin oligodendrocyte glycoprotein (MOG) gene in schizophrenia. Genes Brain Behav 2005;4(1):2-9.
20. Colombo B, Dalla Libera D, Comi G. Brain white matter lesions in migraine: What's the meaning? Neurol Sci 2011;32(1):37-40.
21. Kruit M, Van Buchem M, Launer L, Terwindt G, Ferrari M. Migraine is associated with an increased risk of deep white matter lesions, subclinical posterior circulation infarcts and brain iron accumulation: The population-based MRI camera study. Cephalalgia 2010;30(2):129-36.
22. Atmaca M, Onalan E, Yildirim H, Yuce H, Koc M, Korkmaz S. The association of myelin oligodendrocyte glycoprotein gene and white matter volume in obsessive-compulsive disorder. J Affect Disord 2010;124(3):309-13.