Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in ischemic vascular disease;Polimorfismo C677T del gen de la metilentetrahidrofolato reductasa (MTHFR) en la patología isquémica vascular

Revista de Neurologia

Volumn 43, Issue 10, 2006, Pages 630-636

  Sanchez Marin B ^a   Grasa Ullrich, José María ^b,c,d  

^a HOSPITAL UNIVERSITARIO MIGUEL SERVET   (Spain)

^b UNIVERSITY OF ZARAGOZA   (Spain)

^c Laboratorio de Biología Molecular   (Spain)

^d NONE   (Spain)

Author keywords

Diet; Folate; Homocysteine; MTHFR; Stroke; Transient ischemic attack

Indexed keywords

5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); CYANOCOBALAMIN; FOLIC ACID; VITAMIN B GROUP; HOMOCYSTEINE; METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2);

GENE MUTATION; GENETIC POLYMORPHISM; HOMOZYGOTE; HUMAN; HYPERHOMOCYSTEINEMIA; POPULATION; REVIEW; RISK FACTOR; VASCULAR DISEASE; BRAIN ISCHEMIA; GENETICS;

BRAIN ISCHEMIA; HOMOCYSTEINE; HUMANS; METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2); POLYMORPHISM, GENETIC; RISK FACTORS;

EID: 35348920696     PISSN: 02100010     EISSN: None     Source Type: Journal    
DOI: 10.33588/rn.4310.2005542     Document Type: Review

References (67)

1. Hillier CE, Collins PW, Bowen DJ, Bowley S, Wiles CM. Inherited prothrombotic risk factors and cerebral venous thrombosis. QJM 1998; 91: 677-80.
2. Sánchez-Marín B, Grasa-Ullrich JM, Latorre-Jiménez A, Montañés MA, García-Erce JA, Torres-Gómez M, et al. Hipercoagulabilidad hereditaria y adquirida en pacientes con trombosis venosa cerebral. Neurologia 2002; 17: 405-9.
3. Stolz E, Kemkes-Matthes B, Potzsch B, Hahn M, Kraus J, Wirbartz M. Screening for thrombophilic factors among 25 German patients with cerebral venous thrombosis. Acta Neurol Scand 2000; 102: 31-6.
4. Biousse V, Conard J, Brouzes C, Horellou NH, Ameri A, Bousser MG. Frequency of the 20210 G → A mutation in the 3′-untranslated region of the prothrombin gene in 35 cases of cerebral venous thrombosis. Stroke 1998; 29: 1398-400.
5. Reuner KH, Ruf A, Grau A, Rickmann H, Stolz E, Juttler E, et al. Prothrombin G20210 → A transition is a risk factor for cerebral venous thrombosis. Stroke 1998; 29: 1765-9.
6. Carhuapoma JR, Mitsias P, Levine SR. Cerebral venous thrombosis and anticardiolipin antibodies. Stroke 1997; 28: 2363-9.
7. Souto JC, Coll I, Llobet D, Del Río E, Oliver A, Mateo J, et al. The prothrombin 20210A allele is the most prevalent genetic risk factor for venous thromboembolism in the Spanish population. Thromb Haemost 1998; 80: 366-9.
8. Grasa-Ullrich JM, Torres-Gómez M, Sánchez-Marín B, Marcuello B, García-Erce JA, Giralt-Raichs M. Mutación C677T de la metiltetrahidrofolato reductasa, homocisteína y trombofilia. Rev Clin Esp 2002; 202: 464-5.
9. Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88: 3698-703.
10. Soria JM, Almasy L, Souto JC, Tirado I, Borell M, Mateo J, et al. Linkage analysis demonstrates that the prothrombin G20210A mutation jointly influences plasma prothrombin levels and risk of thrombosis. Blood 2000; 95: 2780-5.
11. Bertina RM, Koeleman BPMC, Koster T, Rosendaal FR, Dirven RJ, De Ronde H, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
12. Koster T, Rosendaal FR, De Ronde F, Briët E, Vandenbroucke JP, Bertina RM. Venous trombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. Lancet 1993; 342: 1503-6.
13. Lalouschek W, Schillinger M, Hsieh K, Endler G, Tentschert S, Lang W, et al. Matched case-control study on factor V Leiden and the prothrombin G20210A mutation in patients with ischemic stroke/transient ischemic attack up to the age of 60 years. Stroke 2005; 36: 1405-9.
14. Wilcken DE, Wilcken B. Free in PMC. The pathogenesis of coronary artery disease. A possible role for methionine metabolism. J Clin Invest 1976; 57: 1079-82.
15. Goyette P, Sumner JS, Milos R, Duncan AMV, Rosenblatt DS, Matthews RG, et al. Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. Nat Genet 1994; 7: 195-200.
16. Goyette P, Pai A, Milos R, Frosst P, Tran P, Chen Z, et al. Gene structure of human and mouse methylenetetrahydrofolate reductase (MTHFR). Mamm Genome 1998; 9: 652-6.
17. Gaughan DJ, Barbaux S, Kluijtmans LA, Whitehead AS. The human and mouse methylenetetrahydrofolate reductase (MTHFR) genes: genomic organization, mRNA structure and linkage to the CLCN6 gene. Gene 2000; 257: 279-89.
18. Goyette P, Christensen B, Rosenblatt DS, Rozen R. Severe and mild mutations in cis for the methylenetetrahydrofolate reductase (MTHFR) gene, and description of five novel mutations in MTHFR. Am J Hum Genet 1996; 59: 1268-75.
19. Goyette P, Frosst P, Rosenblatt DS, Rozen R. Seven novel mutations in the methylenetetrahydrofolate reductase gene and genotype/phenotype correlations in severe methylenetetrahydrofolate reductase deficiency. Am J Hum Genet 1995; 56: 1052-9.
20. Kluijtmans LAJ, Wendel U, Stevens EMB, Van den Heuvel LPWJ, Trijbels FJM, Blom HJ. Identification of four novel mutations in severe methylenetetrahydrofolate reductase deficiency. Eur J Hum Genet 1998; 6: 257-65.
21. Tonetti C, Burtscher A, Bories D, Tulliez M, Zittoun J. Methylenetetrahydrofolate reductase deficiency in four siblings: a clinical, biochemical, and molecular study of the family. Am J Med Genet 2000; 91: 363-7.
22. Beckman DR, Hoganson G, Berlow S, Gilbert EF. Pathological findings in 5,10-methylene tetrahydrofolate reductase deficiency. Birth Defects Orig Artic Ser 1987; 23: 47-64.
23. Selzer RR, Rosenblatt DS, Laxova R, Hogan K. Adverse effect of nitrous oxide in a child with 5,10-methylenetetrahydrofolate reductase deficiency. N Engl J Med 2003; 349: 45-50.
24. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995; 10: 111-3.
25. Van der Put NMJ, Gabreels F, Stevens EMB, Smeitink JAM, Trijbels FJM, Eskes TKAB, et al. A second mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet 1998; 62: 1044-51.
26. Isotalo PA, Wells GA, Donnelly JG. Neonatal and fetal methylenetetrahydrofolate reductase genetic polymorphisms: an examination of C677T and A1298C mutations. Am J Hum Genet 2000; 67: 986-90.
27. Ogino S, Wilson RB. Genotype and haplotype distributions of MTHFR 677C-T and 1298A-C single nucleotide polymorphisms: a meta-analysis. J Hum Genet 2003; 48: 1-7.
28. Schneider JA, Rees DC, Liu YT, Clegg JB. Worldwide distribution of a common methylenetetrahydrofolate reductase mutation. Am J Hum Genet 1998; 62: 1258-60.
29. McAndrew PE, Brandt JT, Pearl DK, Prior TW. The incidence of the gene for thermolabile methylene tetrahydrofolate reductase in African Americans. Thromb Res 1996; 83: 195-8.
30. Stevenson RE, Schwartz CE, Du YZ, Adams MJ. Differences in methylenetetrahydrofolate reductase genotype frequencies, between whites and blacks. Am J Hum Genet 1997; 60: 229-30.
31. Rosenberg N, Murata M, Ikeda Y, Opare-Sem O, Zivelin A, Geffen E, et al. The frequent 5,10-methylenetetrahydrofolate reductase C677T polymorphism is associated with a common haplotype in whites, Japanese, and Africans. Am J Hum Genet 2002; 70: 758-62.
32. Martínez-Frías ML, Bermejo E, Rodríguez-Pinilla E, Scala I, Andria G, Botto L. Frecuencia de la mutación 677C-T del gen de la metilentetrahidrofolato reductasa en una muestra de 652 nacidos vivos españoles. Med Clin (Barc) 2004; 122: 361-4.
33. Grasa-Ullrich J, Torres-Gómez M, Sánchez-Marín B, Calvo-Martín MT, García-Erce JA, Giralt-Raichs M. Hiperhomocisteinemia y mutación 677T de la metiltetrahidrofolato reductasa. An Med Interna 2002; 19: 269.
34. Sánchez-Marín B, Grasa JM, Torres M, Calvo MT, Martínez-Jarreta B, García-Erce JA, et al. Prevalencia de la mutación C677T del gen de la metilentetrahidrofolato reductasa en pacientes con patología isquémica cerebrovascular aguda en la comunidad autónoma aragonesa. An Med Interna 2006; 4: 153-5.
35. Dudman NP, Wilcken DE, Wang J, Lynch JF, Macey D, Lundberg P. Disordered methionine/homocysteine metabolism in premature vascular disease. Its occurrence, cofactor therapy, and enzymology. Arterioscler Thromb Vasc Biol 1993; 12: 1253-60.
36. Perry IJ, Refsum H, Morris RW, Ebrahim SB, Ueland PM, Shaper AG. Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet 1995; 346: 1395-8.
37. Verhoef P, Hennekens CH, Malinow MR, Kok FJ, Willett WC, Stampfer MJ. A prospective study of plasma homocyst(e)ine and risk of ischemic stroke. Stroke 1994; 25: 1924-30.
38. Kelly PJ, Rosand J, Kistler JP, Shih VE, Silveira S, Plomaritoglou A, et al. Homocysteine, MTHFR 677C-T polymorphism, and risk of ischemic stroke: results of a meta-analysis. Neurology 2002; 59: 529-36.
39. Brattström L, Wilcken DE, Ohrvik J. Common MTHFR gene mutation leads hyperhomocysteinemia but no to vascular disease: the results of a metaanalysis. Circulation 1998; 98: 2520.
40. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995; 274: 1049-57.
41. Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 1997; 337: 230-6.
42. Lewis SJ, Ebrahim S, Smith GD. Meta-analysis of MTHFR 677C-T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate? BMJ 2005; 331: 1053-8.
43. Oi S. Current status of prenatal management of fetal spina bifida in the world: world-wide cooperative survey on the medico-ethical issue. Childs Nerv Syst 2003; 19: 596-9.
44. Taguchi H, Kobayashi M, Yoshino N, Hosokawa K. Do Japanese take more folate from traditional Japanese dish than is conventionally estimated? Actual folate contents in hospital diets and marketed lunch boxes. Asian Pac J Cancer Prev 2004; 5: 374-8.
45. Cronin S, Furie KL, Kelly PJ. Dose-related association of MTHFR 677T allele with risk of ischemic stroke: evidence from a cumulative meta-analysis. Stroke 2005; 36: 1581-7.
46. Guttormsen AB, Ueland PM, Nesthus I, Nygard O, Schneede J, Vollset ES, et al. Determinants and vitamin responsiveness of intermediate hyperhomocysteinemia (equal to or greater than 40 micromole/liter): the Hordaland homocysteine study. J Clin Invest 1996; 98: 2174-83.
47. Schwartz SM, Siscovick DS, Malinow R, Rosendaal FR, Beverly RK, Hess DL, et al. Myocardial infarction in young women in relation to plasma total homocysteine, folate and a common variant in the methylenetetrahydrofolate reductasa gene. Circulation 1997; 96: 412-7.
48. Verhoef P, Rimm EB, Hunter DJ, Chen J, Willett WC, Kelsey K, et al. A common mutation in the methylenetetrahydrofolate reductasa gene and risk of coronary heart disease: results among U.S. men. J Am Coll Cardiol 1998; 32: 353-9.
49. Jacques PF, Bostom AG, Williams RR, Ellison RC, Eckfeldt JH, Rosenberg IH, et al. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 1996; 93: 7-9.
50. Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ, Schouten EG. MTHFR 677C-T polymorphism and risk of coronary heart disease: a metaanalysis. JAMA 2002; 288: 2023-31.
51. Gutiérrez JI, Pérez F, Tamparillas M, Grasa JM, Calvo MT, Osuna C, et al. Polimorfismos en los genes de la cistatión-beta-sintasa y en metilentetrahidrofolato reductasa como factores de riesgo para enfermedad vascular cerebral. Med Clin (Barc) 2005; 124: 281-4.
52. Morita H, Taguchi J, Kurihara H, Kitaoka M, Kaneda H, Kurihara Y, et al. Genetic polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease. Circulation 1997; 95: 2032-6.
53. Toole JF, Malinow MR, Chambless LE, Spence JD, Pettigrew LC, Howard VJ, et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the vitamin intervention for stroke prevention (VISP) randomized controlled trial. JAMA 2004; 291: 565-75.
54. Dusitanond P, Eikelboom JW, Hankey GJ, Thom J, Gilmore G, Loh K, et al. Homocysteine-lowering treatment with folic acid, cobalamine and pyridoxine does not reduce blood marker of inflammation, endothelial dysfunction, or hypercoagulability in patients with previous transient ischemic attack or stroke: a randomized substudy of the VITATOPS trial. Stroke 2005; 36: 144-6.
55. Baker F, Picton D, Blackwood S, Hunt J, Erskine M, Dyas M, et al. Blinded comparison of folic acid and placebo in patients with ischemic heart disease: an outcome trial. Circulation 2002; 106 (Suppl 2): 741.
56. Fletcher O, Kessling AM. MTHFR association with arteriosclerotic vascular disease? Hum Genet 1998; 103: 11-21.
57. Ioannidis JP, Ntzani EE, Trikalinos TA. 'Racial' differences in genetic effects for complex diseases. Nat Genet 2004; 36: 1312-8.
58. Sepúlveda-Sánchez JM, Matía-Francés R, Martínez-Salio A, González de la Aleja-Tejera J, Rodríguez-Peña Marín M, Porta-Etessam J. Homocisteína y enfermedad cerebrovascular. Rev Neurol 2004; 38: 347-58.
59. Heijmans BT, Gussekloo J, Kluft C, Droog S, Lagaay AM, Knook DL, et al. Mortality risk in men is associated with a common mutation in the methylene-tetrahydrofolate reductase gene (MTHFR). Eur J Hum Genet 1999; 7: 197-204.
60. Grasa-Ullrich JM, Sánchez-Marín B. Modelo de la intervención antienvejecimiento sobre un sistema influenciado por la genética y la dieta: el sistema metabólico de los folatos. Medicina Antienvejecimiento 2004; 5: 56.
61. International Task Force for the Prevention of Cardiovascular Disease. Homocysteine and cardiovascular disease: recommendations of the International Task Force for the Prevention of Cardiovascular Disease. Nutr Metab Cardiovasc Dis 1998; 8: 212-71.
62. Jacques PF, Selhub J, Bostom AG, Wilson PW, Rosenberg IH. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med 1999; 340: 1449-54.
63. Selhub J, Jacques PF, Bostom AG, Wilson PW, Rosenberg IH. Relationship between plasma homocysteine and vitamin status in the Framingham study population. Impact of folic acid fortification. Public Health Rev 2000; 28: 117-45.
64. Malinow MR, Duell PB, Hess DL, Anderson PH, Kruger WD, Phillipson BE, et al. Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease. N Engl J Med 1998; 338: 1009-15.
65. González-Ordóñez AJ, Medina-Rodríguez JM, Fernández-Álvarez CR, Sánchez-García J, Fernández-Carreira JM, Álvarez-Martínez MV, et al. Reducción de concentraciones elevadas de homocisteína con ácido fólico y vitamina B en pacientes con tromboembolia venosa: relación entre respuesta y genotipo C677T de la metilen tetrahidrofólico reductasa (MTHFR). Med Clin (Barc) 2000; 114: 7-12.
66. Fernández-Moreno MC, Castilla-Guerra L, Castella-Murillo A, Cueli-Rincón B, Fernández-Bolaños R, Gutiérrez-Tous R, et al. Trombosis venosa cerebral en relación con la hiperhomocisteinemia. Rev Neurol 2003; 37: 1040-3.
67. Nelly PJ, Furie KL. Management and prevention of stroke associated with elevated homocysteine. Curr Treat Options Cardiovasc Med 2002; 4: 363-71.