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Plasma homocysteine, MTHFR C677T, CBS 844ins68bp, and MTHFD1 G1958A polymorphisms in spontaneous cervical artery dissections

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Abstract.

Mild hyperhomocysteinemia is a probable risk factor for atherosclerotic diseases and stroke. Recently, associations of elevated plasma homocysteine concentrations in the acute phase and of MTHFR 677 TT genotype with spontaneous cervical artery dissections (sCAD) have been reported. The purpose of this study was to test this hypothesis in the currently largest sample of patients with sCAD, taking into account known factors influencing plasma homocysteine levels. Ninety-five patients with past sCAD were compared with 95 age- and sex-matched healthy individuals. Homocysteine, vitamin B6, B12, folate, and polymorphisms of methylenetetrahydrofolate reductase (MTHFR C677T), cystathionine β-synthase (CBS 844ins68bp) and methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase (MTHFD1 G1958A) were assessed and any associations were analysed using multivariate statistics. The occurrence of sCAD was associated with elevated homocysteine levels with an odds ratio of 1.327 per 20 % percentile. Homocysteine levels were influenced by gender, smoking status, occurrence of hypertension, vitamin B12 and folate levels, and by the MTHFR TT genotype. MTHFR, CBS 844ins68bp, and MTHFD1 G1958A genotype were not independently associated with the occurrence of sCAD. These data suggest that elevated homocysteine is associated with the occurrence of sCAD. The MTHFR C677T polymorphism is associated with the homocysteine level.

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References

  1. Akar N, Akar E, Ozel D, Deda G, Sipahi T (2001) Common mutations at the homocysteine metabolism pathway and pediatric stroke. Thromb Res 102:115–120

    Article  CAS  PubMed  Google Scholar 

  2. Assmann G, Schulte H (1988) The Prospective Cardiovascular Munster (PROCAM) study: prevalence of hyperlipidemia in persons with hypertension and/or diabetes mellitus and the relationship to coronary heart disease. Am Heart J 116:1713–1724

    Article  CAS  PubMed  Google Scholar 

  3. Ay H, Arsava EM, Tokgozoglu SL, Ozer N, Saribas O (2003) Hyperhomocysteinemia is associated with the presence of left atrial thrombus in stroke patients with nonvalvular atrial fibrillation. Stroke 34:909–912

    Article  CAS  PubMed  Google Scholar 

  4. Berger K, Schulte H, Stogbauer F, Assmann G (1998) Incidence and risk factors for stroke in an occupational cohort: the PROCAM Study. Prospective Cardiovascular Muenster Study. Stroke 29:1562–1566

    CAS  PubMed  Google Scholar 

  5. Bogousslavsky J, Pierre P (1992) Ischemic stroke in patients under age 45. Neurol Clin 10:113–124

    CAS  PubMed  Google Scholar 

  6. Brandt T, Orberk E, Weber R, Werner I, Busse O, Muller BT, Wigger F, Grau A, Grond-Ginsbach C, Hausser I (2001) Pathogenesis of cervical artery dissections: association with connective tissue abnormalities. Neurology 57:24–30

    CAS  PubMed  Google Scholar 

  7. Brody LC, Conley M, Cox C, Kirke PN, McKeever MP, Mills JL, Molloy AM, O’Leary VB, Parle-McDermott A, Scott JM, Swanson DA (2002) A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk factor for neural tube defects: report of the Birth Defects Research Group. Am J Hum Genet 71:1207–1215

    Article  CAS  PubMed  Google Scholar 

  8. Cook JW, Taylor LM, Orloff SL, Landry GJ, Moneta GL, Porter JM (2002) Homocysteine and arterial disease. Experimental mechanisms. Vascul Pharmacol 38:293–300

    Article  CAS  PubMed  Google Scholar 

  9. de Bree A, Verschuren W, Bjorke-Monsen A, van der Put N, Heil S, Trijbels F, Blom H (2001) Association between B vitamin intake and plasma homocysteine concentration in the general Dutch population aged 20–65 y. Am J Clin Nutr 77:687–693

    Google Scholar 

  10. de Bree A, Verschuren W, Blom H, Kromhout D (2001) Lifestyle factors and plasma homocysteine concentrations in a general population sample. Am J Epidemiol 154:150–154

    Article  CAS  PubMed  Google Scholar 

  11. de Franchis R, Fermo I, Mazzola G, Sebastio G, Di Minno G, Coppola A, Andria G, D’Angelo A (2000) Contribution of the cystathionine beta-synthase gene (844ins68) polymorphism to the risk of early-onset venous and arterial occlusive disease and of fasting hyperhomocysteinemia. Thromb Haemost 84:576–582

    CAS  PubMed  Google Scholar 

  12. Dziewas R, Konrad C, Drager B, Evers S, Besselmann M, Ludemann P, Kuhlenbaumer G, Stogbauer F, Ringelstein EB (2003) Cervical artery dissections—clinical features, risk factors, therapy and outcome in 126 patients. J Neurol 250:1179–1184

    Article  PubMed  Google Scholar 

  13. Eikelboom JW, Hankey GJ, Anand SS, Lofthouse E, Staples N, Baker RI (2000) Association between high homocyst(e)ine and ischemic stroke due to large- and small-artery disease but not other etiologic subtypes of ischemic stroke. Stroke 31:1069–1075

    CAS  PubMed  Google Scholar 

  14. Ford ES, Smith SJ, Stroup DF, Steinberg KK, Mueller PW, Thacker SB (2002) Homocyst(e)ine and cardiovascular disease: a systematic review of the evidence with special emphasis on casecontrol studies and nested case-control studies. Int J Epidemiol 31:59–70

    Article  PubMed  Google Scholar 

  15. Gallai V, Caso V, Paciaroni M, Cardaioli G, Arning E, Bottiglieri T, Parnetti L (2001) Mild hyperhomocyst(e)inemia: a possible risk factor for cervical artery dissection. Stroke 32:714–718

    CAS  PubMed  Google Scholar 

  16. Geisel J, Zimbelmann I, Schorr H, Knapp JP, Bodis M, Hubner U,Herrmann W (2001) Genetic defects as important factors for moderate hyperhomocysteinemia. Clin Chem Lab Med 39:698–704

    CAS  PubMed  Google Scholar 

  17. Homocysteine Studies Collaboration (2002) Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 288:2015–2022

    PubMed  Google Scholar 

  18. Howard VJ, Sides EG, Newman GC, Cohen SN,Howard G, Malinow MR, Toole JF (2002) Changes in plasma homocyst(e)ine in the acute phase after stroke. Stroke 33:473–478

    Article  CAS  PubMed  Google Scholar 

  19. Husemoen LL, Thomsen TF, Fenger M, Jorgensen HL, Jorgensen T (2003) Contribution of thermolabile methylenetetrahydrofolate reductase variant to total plasma homocysteine levels in healthy men and women. Genet Epidemiol 24:322–330

    Article  PubMed  Google Scholar 

  20. Jacques PF, Bostom AG, Wilson PW, Rich S, Rosenberg IH, Selhub J (2001) Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort. Am J Clin Nutr 73:613–621

    CAS  PubMed  Google Scholar 

  21. Kelly PJ, Furie KL, Kistler JP, Barron M, Picard EH, Mandell R, Shih VE (2003) Stroke in young patients with hyperhomocysteinemia due to cystathionine beta-synthase deficiency. Neurology 60:275–279

    CAS  PubMed  Google Scholar 

  22. Kelly PJ, Rosand J, Kistler JP, Shih VE, Silveira S, Plomaritoglou A, Furie KL (2002) Homocysteine, MTHFR 677C → T polymorphism, and risk of ischemic stroke: results of a meta-analysis. Neurology 59:529–536

    Google Scholar 

  23. Kristensen B, Malm J, Carlberg B, Stegmayr B, Backman C, Fagerlund M, Olsson T (1997) Epidemiology and etiology of ischemic stroke in young adults aged 18 to 44 years in northern Sweden. Stroke 28:1702–1709

    CAS  PubMed  Google Scholar 

  24. Lim U, Cassano P (2002) Homocysteine and blood pressure in the Third National Health and Nutrition Examination Survey, 1988–1994. Am J Epidemiol 156:1105–1113

    Article  PubMed  Google Scholar 

  25. Lindgren A, Brattstrom L, Norrving B, Hultberg B, Andersson A, Johansson BB (1995) Plasma homocysteine in the acute and convalescent phases after stroke. Stroke 26:795–800

    CAS  PubMed  Google Scholar 

  26. Moller J, Nielsen GM, Tvedegaard KC, Andersen NT, Jorgensen PE (2000) A meta-analysis of cerebrovascular disease and hyperhomocysteinaemia. Scand J Clin Lab Invest 60:491–499

    Article  CAS  PubMed  Google Scholar 

  27. Nygard O, Refsum H, Ueland PM, Vollset SE (1998) Major lifestyle determinants of plasma total homocysteine distribution: the Hordaland Homocysteine Study. Am J Clin Nutr 67:263–270

    CAS  PubMed  Google Scholar 

  28. Pezzini A, Del Zotto E, Archetti S, Negrini R, Bani P, Albertini A, Grassi M, Assanelli D, Gasparotti R, Vignolo LA, Magoni M, Padovani A (2002) Plasma homocysteine concentration, C677T MTHFR genotype, and 844ins68bp CBS genotype in young adults with spontaneous cervical artery dissection and atherothrombotic stroke. Stroke 33:664–669

    Article  CAS  PubMed  Google Scholar 

  29. Saw SM, Yuan JM, Ong CN, Arakawa K, Lee HP, Coetzee GA, Yu MC (2001) Genetic, dietary, and other lifestyle determinants of plasma homocysteine concentrations in middle-aged and older Chinese men and women in Singapore. Am J Clin Nutr 73:232–239

    CAS  PubMed  Google Scholar 

  30. Schievink WI, Mokri B, Whisnant JP (1993) Internal carotid artery dissection in a community. Rochester, Minnesota, 1987–1992. Stroke 24:1678–1680

    CAS  PubMed  Google Scholar 

  31. Tsai MY, Bignell M, Yang F, Welge BG, Graham KJ, Hanson NQ (2000) Polygenic influence on plasma homocysteine: association of two prevalent mutations, the 844ins68 of cystathionine beta-synthase and A(2756)G of methionine synthase,with lowered plasma homocysteine levels. Atherosclerosis 149:131–137

    Article  CAS  PubMed  Google Scholar 

  32. Zhang G, Dai C (2001) Gene polymorphisms of homocysteine metabolismrelated enzymes in Chinese patients with occlusive coronary artery or cerebral vascular diseases. Thromb Res 104:187–195

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Dept. of Neurology, University of Münster, Albert-Schweitzer-Str. 11, 48149, Münster, Germany

    Carsten Konrad MD, Georg A. Müller, Gregor Kuhlenbäumer MD, Darius G. Nabavi MD, Rainer Dziewas MD, Florian Stögbauer MD & Erich B. Ringelstein MD

  2. Dept. of Psychiatry, University of Münster, Albert-Schweitzer-Str. 11, 48149, Münster, Germany

    Carsten Konrad MD

  3. Institute of Arteriosclerosis Research, University of Münster, Domagkstr. 3, 48149, Münster, Germany

    Claus Langer PhD, Gregor Kuhlenbäumer MD, Erich B. Ringelstein MD & Ralf Junker MD

  4. Institute of Clinical Chemistry and Laboratory Medicine, University of Münster, Albert-Schweitzer-Str. 33, 48129, Münster, Germany

    Claus Langer PhD & Ralf Junker MD

  5. Institute of Epidemiology, University of Münster, Albert-Schweitzer-Str. 33, 48129, Münster, Germany

    Klaus Berger MD, PhD

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  1. Carsten Konrad MD
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  2. Georg A. Müller
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Correspondence to Carsten Konrad MD.

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Konrad, C., Müller, G.A., Langer, C. et al. Plasma homocysteine, MTHFR C677T, CBS 844ins68bp, and MTHFD1 G1958A polymorphisms in spontaneous cervical artery dissections. J Neurol 251, 1242–1248 (2004). https://doi.org/10.1007/s00415-004-0523-z

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  • DOI: https://doi.org/10.1007/s00415-004-0523-z

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