ONE-CARBON METABOLISM GENE POLYMORPHISM CORRELATE WITH LEVELS OF DNA METHYLTRANSFERASES IN PATIENTS WITH MIGRAINE

NINO KRAVEISHVILI; EKA KVARATSHELIA; SANDRO SURMAVA; MAIA GAGUA; EKA MAISURADZE; ELENE ABZIANIDZE

doi:10.52340/jecm.2023.01.12

ONE-CARBON METABOLISM GENE POLYMORPHISM CORRELATE WITH LEVELS OF DNA METHYLTRANSFERASES IN PATIENTS WITH MIGRAINE

Authors

NINO KRAVEISHVILI
EKA KVARATSHELIA
SANDRO SURMAVA
MAIA GAGUA
EKA MAISURADZE
ELENE ABZIANIDZE

DOI:

https://doi.org/10.52340/jecm.2023.01.12

Keywords:

DNA, Migraine, Methylation, DNMT, correlation

Abstract

Migraine is a common, disabling disorder characterized by attacks of 4 to 72 h of severe headache and associated autonomic and neurological symptoms. In the present study we analyzed the expression of DNMT1, DNMT3a, and DNMT3b in patients with migraine compared with healthy controls as well as the association between the levels of DNMTs and the LINE-1 methylation status in migraine patients with MTHFR C677T variant. Materials and Method: A total 48 individuals were enrolled in this study (24 patients with migraine and 24 age-matched healthy controls). The study protocol was approved by the Ethics Committee of Tbilisi State Medical University.

Results: We observed that methylation of LINE-1 were correlated with the levels of DNMT3a in migraine. In addition, levels of DNMT1, DNMT3a and DNMT3b in patients with TT genotypes of MTHFR gene rs1801133 polymorphism were significantly lower compared with individuals with CC genotypes. Conclusions: Differential levels DNMTs may play an important role in the pathogenesis of migraine. Further investigation of enzymes involved in DNA methylation with larger number of samples may provide important insight into the development of novel treatments for episodic and/or chronic migraine.

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References

Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition (beta version). Cephalalgia. 2013; 33:629-808. doi: 10.1177/0333102413485658

Peters GL. Migraine overview and summary of current and emerging treatment options. Am J Manag Care 2019 Jan 1;25(2 Suppl):S23-34.

Scher AI, Stewart WF, Lipton RB. Migraine and headache: a meta-analytic approach. In: Crombie IK, ed. Epidemiology of pain. Seattle, WA, IASP Press, 1999; 159-170.

Steiner TJ, Scher AI, Stewart WF, Kolodner K, Liberman J, Lipton RB. The prevalence and disability burden of adult migraine in England and their relationships to age, gender and ethnicity. Cephalalgia. 2003; 23:519-527. doi: 10.1046/j.1468-2982.2003.00568.x

Kowalska M., Prendecki M., Kozubski W., Lianeri M., Dorszewska J. Molecular factors in migraine. Oncotarget. 2016; 7: 50708-50718.

Granella F, Sances G, Allais G, Nappi RE, Tirelli A, Benedetto C, Brundu B, Facchinetti F, Nappi G. Characteristics of menstrual and nonmenstrual attacks in women with menstrually related migraine referred to headache centres. Cephalalgia. 2004; 24: 707-716. doi: 10.1111/j.1468-2982.2004.00741.x

Rainero I, Vacca A, Roveta F, et al. Targeting MTHFR for the treatment of migraines. Expert Opinion on Therapeutic Targets 2019; 23: 29–37.

Liu L, Yu Y, He J, et al. Effects of MTHFR C677T and A1298C polymorphisms on migraine susceptibility: A meta‐analysis of 26 studies. Headache: The Journal of Head and Face Pain 2019; 59: 891–905.

Fila M, Chojnacki C, Chojnacki J, et al. Is an “epigenetic diet” for migraines justified? the case of folate and DNA methylation. Nutrients 2019; 11: 2763.

Crider KS, Yang TP, Berry RJ, et al. Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate's role. Advances in nutrition 2012 Jan;3(1):21-38.

Castro R, Rivera I, Ravasco P, et al. 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C->t and 1298a->C mutations are associated with DNA hypomethylation. Journal of Med Genetics 2004;41:454-8.

Yakub M, Moti N, Parveen S, Chaudhry B, Azam I, Iqbal MP. Polymorphisms in MTHFR, MS and CBS genes and homocysteine levels in a Pakistani population. PLoS One. 2012;7(3):e33222. doi: 10.1371/journal.pone.0033222. Epub 2012 Mar 21. PMID: 22470444; PMCID: PMC3310006.

Smith ZD and Meissner A: DNA methylation: Roles in mammalian development. Nat Rev Genet. 2013; 14:204–220.

Moore LD, Le T, Fan G: DNA methylation and its basic function. Neuropsychopharmacology. 2013; 38:23–38.

Loo SK, Ab Hamid SS, Musa M, Wong KK: DNMT1 is associated with cell cycle and DNA replication gene sets in diffuse large B-cell lymphoma. Pathol Res Pract. 2018; 214:134–143.

Kraveishvili N, Kvaratskhelia E, Surmava S, et al. DNA methylation status of interspersed repetitive sequences in patients with migraine. Journal of International Medical Research. 2023;51(2).

Robertson KD. DNA methylation and human disease. Nat Rev Genet. 2005 Aug;6(8):597–610.

Kareta MS, Botello ZM, Ennis JJ, Chou C, Chedin F. Reconstitution and mechanism of the stimulation of de novo methylation by human DNMT3L. J Biol Chem. 2006 Sep 8;281(36):25893–25902.

Yoder JA, Walsh CP, Bestor TH. Cytosine methylation and the ecology of intragenomic parasites. Trends Genet. 1997 Aug;13(8):335–340.

Kitkumthorn N, Keelawat S, Rattanatanyong P, Mutirangura A. LINE-1 and Alu Methylation Patterns in Lymph Node Metastases of Head and Neck Cancers. Asian Pacific Journal of Cancer Prevention. Asian Pacific Organization for Cancer Prevention; 2012; 13:4469–75.

Eising E, A Datson N, Van Den Maagdenberg AMJM, et al. Epigenetic mechanisms in Migraine: A promising avenue? BMC Medicine 2013; 11. Epub ahead of print 2013. doi: 10.1186/1741-7015-11-26.