Polymorphism of methylenetetrahydrofolate reductase (MTHFR) folate metabolism gene and hyperhomocysteinemia in migraine
Keywords:
methylenetetrahydrofolate reductase (МТHFR), migraine, folate cycle genes, homocysteine, hyperhomocysteinemia, targeted therapy
Abstract
The review discusses the role of polymorphism of the methylenetetrahydrofolate reductase (MTHFR) folate metabolism gene responsible for hyperhomocysteinemia in the pathogenesis of migraine. Data on the polymorphism of the folate cycle gene C677 and homocysteine metabolism are presented. The pathogenetic mechanism of migraine associated with proinflammatory, procoagulant properties of homocysteine and with the activation of oxidative stress, endothelial dysfunction, and neurogenic inflammation related with increased concentrations of homocysteine is described. Prospects and social significance of implementing data of genetic research into clinical practice are discussed. Included is the role of genetic research in predicting the course and complications of migraine, in assessment of risk for complications, and in pharmacotherapeutic approaches to migraine treatment. Methods. MEDLINE, SCOPUS and Web of Science databases were used to search for data: MTHFR, migraine, pathophysiology, hyperhomocysteinemia, targeted therapy.
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References
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4. Victor T.W., Hu X., Campbell J.C., Buse D.C, Lipton R.B. Migraine prevalence by age and sex in the United States: a life-span study. Cephalalgia. 2010; 30(9): 1065-1072. https://doi.org/10.1177/0333102409355601
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7. Sergeev A.V., Ekusheva E.V. Migraine in children. Features of diagnostics and modern possibilities of therapy. Russkiy meditsinskiy zhurnal. Meditsinskoeobozrenie. 2018; 2: 26-32
8. De Vries B., Frants R., Ferrari M. Molecular genetics of migraine. Hum. Genet. 2009; 126: 115-132. https://doi.org/ 10.1007/s.00439-009-0684-z
9. Joutel A., Bousser M.G., Biousse V., Labauge P., Chabriat H., Nibbio A. et al. A gene for familial hemiplegic migraine maps to chromosome 19. Nat. Genet. 1993; 5: 40-45. https://doi.org/ 10.104/j.1468-2982.1996.1603135-3.x
10. Champe P., Harvey R. Biochemistry. Lippincott’s Illustrated Reviews. 4th edit. Philadelphia: Lippincott Williams and Wilkins. 2008; 261-276.
11. McCully K.S. Chemical Pathology of Homocysteine. Excitotoxicity, Oxidative Stress, Endothelial Dysfunction, and Inflammation. AnnClin. Lab. Sci. 2009; 39(3): 219-232.
12. Pizova N. V., Pizov N. A. Hyperhomocysteinemia and ischemic stroke. Meditsinskiy sovet. 2017; 10: 12-16
13. Dietrich-Muszalska A., Malinowska J., Olas B., Glowacki R., Bald E., Wachowicz B. et al. The oxidative stress may be induced by the elevated homocysteine in schizophrenic patients. Neurochem. Res. 2012; 37(5): 1057-1062. https://doi.org/10.1007/s.11064-012-0707-3.
14. Froese D.S., Kopec J, Rembeza E, Bezerra G.A., Oberholzer A.E., Suormala T. et al. Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition. Nat. Commun. 2018; 9(1): 2261. https://doi.org/ 10.1038/s.41467-018-04735-2
15. Tufkova S., Paskaleva D., Sandeva M. Acute exogenous intoxications and homocysteine Folia Medica. 2020; 62: 519-524. https://doi.org/10.3897/folmed.62.e49220
16. Mudd S., Finkelstein J., Irreverre F., Laster L. Homocystinuria: An enzymatic defect. Science. 1964; 143: 1443-1445. https://doi.org/10.1126/SCIENCE. 143.3613.1443
17. Tadtaeva Z.G. Hyperhomocysteinemia (НHс) in migraine in children (review). Zdorov'e–osnova chelovecheskogo potentsiala: problemy i puti ikh resheniya. 2012; 7(2): 721-729. (In Russian)
18. Petrishchev N.N. Endothelial dysfunction. Pathogenetic significance and methods of correction. SPbIITsVMA. 2007. (In Russian)
19. Van de Ven R.C.G., Kaja S., Plomp J. Genetic Models of migraine. Arch. Neurol. 2007; 64: 643-646. https://doi.org/10.1001/archneur.64.5.643
20. Abushik P.A., Niittykoski M., Giniatullina R.,Shakirzyanova A., Bart G., Fayuk D.et al. The role of NMDA and mGluR5 receptors in calcium mobilization and neurotoxicity of homocysteine in trigeminal and cortical neurons and glial cells. J. Neurochem. 2014; 129: 264–274. https://doi.org/DOI: 10.1111/jnc. 12615
21. Lea R.A., Ovcaric M., Sundholm J., MacMillan J., Griffiths L.R. The methylenetetrahydrofolate reductase gene variant C677T influences susceptibility to migraine with aura. BMCMedicine. 2004; 2: 3. https://doi.org/10.1186/1741-7015-2-3
22. NoskovaT.Yu., ShvedkovV.V., KrasnikovA.V., ShabalinaA.A., KostyrevaM.V., AbaimovD.A. i dr. Hyperhomocysteinemia and brain white matter lesion in patients with epilepsy: an analysis of two cases. VestnikRossiyskoyvoenno-meditsinskoyakademii. 2018; S3: 97-99. https://doi.org/10.17816/bmma13223. (In Russian)
23. TadtaevaZ.G., KatsadzeYu.L. Polymorphism of the methylenetetrahydrofolate reductase gene, hyperhomocysteinemia, and the possibility of its drug correction in migraine in children. Kazanskiy meditsinskiy zhurnal. 2007; 88 (1): 16-20. (In Russian)
24. Kowa H., Yasui K., Takeshima T. The homozygous C677T mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for migraine. Am. J. Med. Genet. 2000; 96: 762-764. https://doi.org/ 10.1002/1096-8628(20001)96:6<762::aid-ajmg12>3.0co;2-x
25. Tadtaeva Z.G. Genetics of migraine. Literature review. VestnikSankt-Peterburgskogouniversiteta. 2013; 11(1): 70-80. (In Russian)
26. Kaunisto M.A., Kattela M., Hämäläinen E. Testing of variants of the MTHFR and EDR1 genes in 1798 Finnish individuals fails to conform the association with migraine with aura. Cephalalgia. 2006; 26: 1462-1472. https://doi.org/ 10.1111/j.1468-2982.2006.1228.x
27. Lea R.A., Ovcaric M., Sundholm J., MacMillan J., Griffiths L.R. The methylenetetrahydrofolate reductase gene variant C677T influences susceptibility to migraine with aura. BMC Medicine. 2004; 2: 3. https://doi.org/ 10.1186/1741-7015-2-3.
28.Ligthart L., de Vries B., Smith A.V., Ikram M.A., Amin N., Hottenga J-J. Meta-analysis of genome-wide association for migraine in six population-based European cohortы. Eur J Hum Genet. 2011; 19(8): 901-907. https://doi.org/10.1038/ejhg.2011.48
29. Milutinovic S., D’Alessio A.C., Detich N. Valproate induces widespread epigenetic reprogramming which involves demethylation of specific genes. Carcinogenesis. 2007; 28: 560–571. https://doi.org/10.1093/carcin/bgI167
30. Rubino E., Ferrero M., Rainero I. Association of the C677T polymorphism in the MTHFR gene with migraine: a meta-analysis. Cephalalgia. 2009; 29: 818-825. https://doi.org/ 10.1111/j.1468-2982.2007.01400.x
31. Samaan Z., Gaysina D., Cohen-Woods S., Craddock N., Jones L., Korszun A. et al. Methylenetetrahydrofolate reductase gene variant (MTHFR C677T) and migraine: a case control study and meta-analysis. BMC Neurol. 2011; 11: 66. https://doi.org/ 10.1177/0333102416638520
32. Schürks M., Rist P.M., Kurth T. MTHFR 677C/T and D/I polymorphisms in migraine: a systematic review and meta-analysis. Headache. 2009; 50: 588-599. https://doi.org/ 10.1111/head.12798
33. Liu A., Menon S., Colson N.J., Quinlan S., Cox H., Peterson M. et al. Analysis of the MTHFR C677T variant with migraine phenotypes. BMC Res Notes. 2010; 3: 213. https://doi.org/10.1186/1756-0500-3-213.
34. Azimova Yu.E., Klimov E.A., Naumova E.A., Kokaeva Z.G., Zaytseva A.I., Kondrat'eva N.S., i dr. Combined genotypes of genes encoding proteins of the cholecystokinergic system and folate cycle enzymes are largely associated with migraine. Patologicheskayafiziologiyaieksperimental'nayaterapiya. 2020; 64: 5-14. (In Russian)
35. Hademenos G.., Alberts M.., Award I., Mayberg M., Shephard T., Jagoda A., et al. Advances in the genetics of cerebrovascular disease and stroke. .Neurology. 2001; 56 (8): 125 https://doi.org/10.1212/WNL.56.8.997
36. Moschiano F., D'Amico D., Ciusani E., Erba N., Rigamonti A., Schieroni F. et al. Coagulation abnormalities in migraine and ischaemic cerebrovascular disease: a link between migraine and ischaemic stroke. Neurol. Sci. 2004; 25 (suppl.3.):126–128. https://doi.org/10.1001/s10072-004-0269-5
37. AzimovaYu.E., TabeevaG.R., KlimovE.A. Genetics of migraine. Annaly klinicheskoy i eksperimental'noy nevrologii. 2008; 2(1): 41-46. (In Russian)
38. PizovaN.V., PizovN.A. Hyperhomocysteinemia and ischemic stroke. Meditsinskiy sovet. 2017; 10: 12-16. (In Russian)
39. Zhong C., Xu T., Peng Y., Wang A., Wang J., Peng H. et al. Plasma Homocysteine and Prog nosis of Acute Ischemic Stroke: а Gender-Specific Analysis From CATIS Randomized Clinical Trial. Mol Neurobiol. 2017; 54(3): 2022-2030. https://doi.org/ 10.1007/s12035-016-9799-0;
40. Han L., Wu Q., Wang C., Hao Y., Zhao J., Zhang .L. et al. Homocysteine, Ischemic Stroke, and Coronary Heart Disease in Hyper tensive Patients: A Population-Based, Prospective Cohort Study. Stroke. 2015; 46: 1777-1786. https://doi.org/10.1016/j.amjcard.2008.02.056
41. De Tommaso M., Difruscolo O., Sardaro M., Libro G., Pecoraro C., Serpino C. et al. Influence of MTHFR genotype on contingent negative variation and MRI abnormalities in migraine. Headache. 2007; 47: 253-265. https://doi.org/ 10.1111/j1526-4610.2006.00690.x
2. Tabeeva G.R., Yakhno N.N. Migraine. Moscow; Geotar-Media; 2011. (In Russian)
3. Global, regional, and national burden of neurological disorders during 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015 Neurological Disorders Collaborator Group. Lancet Neurol. 2017; 16: 877- 897. https://doi.org/ 10.1016/S1474-4422(17)30299-5
4. Victor T.W., Hu X., Campbell J.C., Buse D.C, Lipton R.B. Migraine prevalence by age and sex in the United States: a life-span study. Cephalalgia. 2010; 30(9): 1065-1072. https://doi.org/10.1177/0333102409355601
5. Elser J.M., Woody R.C. Migraine headache in the infant and young child. Headache. 1990; 30(6): 366-368. https://doi.org/ 10.1111/j.1526-4610.1990.hed30063.x
6. Rachin A.P., Yudel'son Ya.B., SergeevA.V. Epidemiology of chronic daily headache in children and adolescents. Bol'. 2004; 2(3): 27-30. (In Russian)
7. Sergeev A.V., Ekusheva E.V. Migraine in children. Features of diagnostics and modern possibilities of therapy. Russkiy meditsinskiy zhurnal. Meditsinskoeobozrenie. 2018; 2: 26-32
8. De Vries B., Frants R., Ferrari M. Molecular genetics of migraine. Hum. Genet. 2009; 126: 115-132. https://doi.org/ 10.1007/s.00439-009-0684-z
9. Joutel A., Bousser M.G., Biousse V., Labauge P., Chabriat H., Nibbio A. et al. A gene for familial hemiplegic migraine maps to chromosome 19. Nat. Genet. 1993; 5: 40-45. https://doi.org/ 10.104/j.1468-2982.1996.1603135-3.x
10. Champe P., Harvey R. Biochemistry. Lippincott’s Illustrated Reviews. 4th edit. Philadelphia: Lippincott Williams and Wilkins. 2008; 261-276.
11. McCully K.S. Chemical Pathology of Homocysteine. Excitotoxicity, Oxidative Stress, Endothelial Dysfunction, and Inflammation. AnnClin. Lab. Sci. 2009; 39(3): 219-232.
12. Pizova N. V., Pizov N. A. Hyperhomocysteinemia and ischemic stroke. Meditsinskiy sovet. 2017; 10: 12-16
13. Dietrich-Muszalska A., Malinowska J., Olas B., Glowacki R., Bald E., Wachowicz B. et al. The oxidative stress may be induced by the elevated homocysteine in schizophrenic patients. Neurochem. Res. 2012; 37(5): 1057-1062. https://doi.org/10.1007/s.11064-012-0707-3.
14. Froese D.S., Kopec J, Rembeza E, Bezerra G.A., Oberholzer A.E., Suormala T. et al. Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition. Nat. Commun. 2018; 9(1): 2261. https://doi.org/ 10.1038/s.41467-018-04735-2
15. Tufkova S., Paskaleva D., Sandeva M. Acute exogenous intoxications and homocysteine Folia Medica. 2020; 62: 519-524. https://doi.org/10.3897/folmed.62.e49220
16. Mudd S., Finkelstein J., Irreverre F., Laster L. Homocystinuria: An enzymatic defect. Science. 1964; 143: 1443-1445. https://doi.org/10.1126/SCIENCE. 143.3613.1443
17. Tadtaeva Z.G. Hyperhomocysteinemia (НHс) in migraine in children (review). Zdorov'e–osnova chelovecheskogo potentsiala: problemy i puti ikh resheniya. 2012; 7(2): 721-729. (In Russian)
18. Petrishchev N.N. Endothelial dysfunction. Pathogenetic significance and methods of correction. SPbIITsVMA. 2007. (In Russian)
19. Van de Ven R.C.G., Kaja S., Plomp J. Genetic Models of migraine. Arch. Neurol. 2007; 64: 643-646. https://doi.org/10.1001/archneur.64.5.643
20. Abushik P.A., Niittykoski M., Giniatullina R.,Shakirzyanova A., Bart G., Fayuk D.et al. The role of NMDA and mGluR5 receptors in calcium mobilization and neurotoxicity of homocysteine in trigeminal and cortical neurons and glial cells. J. Neurochem. 2014; 129: 264–274. https://doi.org/DOI: 10.1111/jnc. 12615
21. Lea R.A., Ovcaric M., Sundholm J., MacMillan J., Griffiths L.R. The methylenetetrahydrofolate reductase gene variant C677T influences susceptibility to migraine with aura. BMCMedicine. 2004; 2: 3. https://doi.org/10.1186/1741-7015-2-3
22. NoskovaT.Yu., ShvedkovV.V., KrasnikovA.V., ShabalinaA.A., KostyrevaM.V., AbaimovD.A. i dr. Hyperhomocysteinemia and brain white matter lesion in patients with epilepsy: an analysis of two cases. VestnikRossiyskoyvoenno-meditsinskoyakademii. 2018; S3: 97-99. https://doi.org/10.17816/bmma13223. (In Russian)
23. TadtaevaZ.G., KatsadzeYu.L. Polymorphism of the methylenetetrahydrofolate reductase gene, hyperhomocysteinemia, and the possibility of its drug correction in migraine in children. Kazanskiy meditsinskiy zhurnal. 2007; 88 (1): 16-20. (In Russian)
24. Kowa H., Yasui K., Takeshima T. The homozygous C677T mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for migraine. Am. J. Med. Genet. 2000; 96: 762-764. https://doi.org/ 10.1002/1096-8628(20001)96:6<762::aid-ajmg12>3.0co;2-x
25. Tadtaeva Z.G. Genetics of migraine. Literature review. VestnikSankt-Peterburgskogouniversiteta. 2013; 11(1): 70-80. (In Russian)
26. Kaunisto M.A., Kattela M., Hämäläinen E. Testing of variants of the MTHFR and EDR1 genes in 1798 Finnish individuals fails to conform the association with migraine with aura. Cephalalgia. 2006; 26: 1462-1472. https://doi.org/ 10.1111/j.1468-2982.2006.1228.x
27. Lea R.A., Ovcaric M., Sundholm J., MacMillan J., Griffiths L.R. The methylenetetrahydrofolate reductase gene variant C677T influences susceptibility to migraine with aura. BMC Medicine. 2004; 2: 3. https://doi.org/ 10.1186/1741-7015-2-3.
28.Ligthart L., de Vries B., Smith A.V., Ikram M.A., Amin N., Hottenga J-J. Meta-analysis of genome-wide association for migraine in six population-based European cohortы. Eur J Hum Genet. 2011; 19(8): 901-907. https://doi.org/10.1038/ejhg.2011.48
29. Milutinovic S., D’Alessio A.C., Detich N. Valproate induces widespread epigenetic reprogramming which involves demethylation of specific genes. Carcinogenesis. 2007; 28: 560–571. https://doi.org/10.1093/carcin/bgI167
30. Rubino E., Ferrero M., Rainero I. Association of the C677T polymorphism in the MTHFR gene with migraine: a meta-analysis. Cephalalgia. 2009; 29: 818-825. https://doi.org/ 10.1111/j.1468-2982.2007.01400.x
31. Samaan Z., Gaysina D., Cohen-Woods S., Craddock N., Jones L., Korszun A. et al. Methylenetetrahydrofolate reductase gene variant (MTHFR C677T) and migraine: a case control study and meta-analysis. BMC Neurol. 2011; 11: 66. https://doi.org/ 10.1177/0333102416638520
32. Schürks M., Rist P.M., Kurth T. MTHFR 677C/T and D/I polymorphisms in migraine: a systematic review and meta-analysis. Headache. 2009; 50: 588-599. https://doi.org/ 10.1111/head.12798
33. Liu A., Menon S., Colson N.J., Quinlan S., Cox H., Peterson M. et al. Analysis of the MTHFR C677T variant with migraine phenotypes. BMC Res Notes. 2010; 3: 213. https://doi.org/10.1186/1756-0500-3-213.
34. Azimova Yu.E., Klimov E.A., Naumova E.A., Kokaeva Z.G., Zaytseva A.I., Kondrat'eva N.S., i dr. Combined genotypes of genes encoding proteins of the cholecystokinergic system and folate cycle enzymes are largely associated with migraine. Patologicheskayafiziologiyaieksperimental'nayaterapiya. 2020; 64: 5-14. (In Russian)
35. Hademenos G.., Alberts M.., Award I., Mayberg M., Shephard T., Jagoda A., et al. Advances in the genetics of cerebrovascular disease and stroke. .Neurology. 2001; 56 (8): 125 https://doi.org/10.1212/WNL.56.8.997
36. Moschiano F., D'Amico D., Ciusani E., Erba N., Rigamonti A., Schieroni F. et al. Coagulation abnormalities in migraine and ischaemic cerebrovascular disease: a link between migraine and ischaemic stroke. Neurol. Sci. 2004; 25 (suppl.3.):126–128. https://doi.org/10.1001/s10072-004-0269-5
37. AzimovaYu.E., TabeevaG.R., KlimovE.A. Genetics of migraine. Annaly klinicheskoy i eksperimental'noy nevrologii. 2008; 2(1): 41-46. (In Russian)
38. PizovaN.V., PizovN.A. Hyperhomocysteinemia and ischemic stroke. Meditsinskiy sovet. 2017; 10: 12-16. (In Russian)
39. Zhong C., Xu T., Peng Y., Wang A., Wang J., Peng H. et al. Plasma Homocysteine and Prog nosis of Acute Ischemic Stroke: а Gender-Specific Analysis From CATIS Randomized Clinical Trial. Mol Neurobiol. 2017; 54(3): 2022-2030. https://doi.org/ 10.1007/s12035-016-9799-0;
40. Han L., Wu Q., Wang C., Hao Y., Zhao J., Zhang .L. et al. Homocysteine, Ischemic Stroke, and Coronary Heart Disease in Hyper tensive Patients: A Population-Based, Prospective Cohort Study. Stroke. 2015; 46: 1777-1786. https://doi.org/10.1016/j.amjcard.2008.02.056
41. De Tommaso M., Difruscolo O., Sardaro M., Libro G., Pecoraro C., Serpino C. et al. Influence of MTHFR genotype on contingent negative variation and MRI abnormalities in migraine. Headache. 2007; 47: 253-265. https://doi.org/ 10.1111/j1526-4610.2006.00690.x
Published
2021-12-11
How to Cite
Tadtaeva Z., Yakovleva . E., Amelin A. Polymorphism of methylenetetrahydrofolate reductase (MTHFR) folate metabolism gene and hyperhomocysteinemia in migraine // Patologicheskaya Fiziologiya i Eksperimental’naya Terapiya (Pathological physiology and experimental therapy). 2021. VOL. 65. № 4. PP. 109–115.
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Reviews
