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Blood, 15 November 2004, Vol. 104, No. 10, pp. 3046-3051. Prepublished online as a Blood First Edition Paper on June 29, 2004; DOI 10.1182/blood-2004-03-0897. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-0897v1 104/10/3046    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Frederiksen, J. Articles by Nordestgaard, B. G. Search for Related Content PubMed PubMed Citation Articles by Frederiksen, J. Articles by Nordestgaard, B. G. Related Collections Clinical Trials and Observations Hemostasis, Thrombosis, and Vascular Biology Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Methylenetetrahydrofolate reductase polymorphism (C677T), hyperhomocysteinemia, and risk of ischemic cardiovascular disease and venous thromboembolism: prospective and case-control studies from the Copenhagen City Heart Study Jeppe Frederiksen, Klaus Juul, Peer Grande, Gorm B. Jensen, Torben V. Schroeder, Anne Tybjærg-Hansen, and Børge G. Nordestgaard From the Department of Clinical Biochemistry, Herlev University Hospital; the Department of Medicine B, Rigshospitalet, Copenhagen University Hospital; The Copenhagen City Heart Study, Bispebjerg University Hospital; and the Department of Vascular Surgery and Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, University of Copenhagen, Denmark. Hyperhomocysteinemia is associated with ischemic cardiovascular disease (ICD) and venous thromboembolism (VTE). We tested the hypothesis that methylenetetrahydrofolate reductase (MTHFR) C677T homozygosity with hyperhomocysteinemia is associated with ICD and VTE. First, 9238 randomly selected whites from the general population were followed for 23 years. Second, 2125 whites with ischemic heart disease and 836 whites with ischemic cerebrovascular disease were compared with 7568 controls from the general population. Plasma homocysteine was elevated 25% in homozygotes versus noncarriers (P < .001) and 19% in ICD/VTE cases versus controls (P < .001). In prospective studies adjusted hazard ratios for ICD and VTE for homozygotes versus noncarriers did not differ from 1.0. Furthermore, MTHFR C677T homozygosity was not associated with increased risk of ICD or VTE in subgroups after stratification for sex, age, cholesterol, high-density lipoprotein cholesterol, lipoprotein(a), fibrinogen, triglycerides, body mass index, smoking, diabetes mellitus, hypertension, and factor V Leiden genotype. Finally, in case-control studies odds ratios for ischemic heart disease and ischemic cerebrovascular disease in homozygotes versus noncarriers did not differ from 1.0. In conclusion, MTHFR C677T homozygosity with hyperhomocysteinemia is not associated with ICD or VTE; however, ICD/VTE is associated with hyperhomocysteinemia. Therefore, ICD and VTE may cause hyperhomocysteinemia, rather than vice versa. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Hyperhomocysteinemia: cause or effect of disease? Rossella Marcucci, Anna Maria Gori, Rosanna Abbate, Jeppe Frederiksen, Klaus Juul, Anne Tybjærg-Hansen, and Børge G. Nordestgaard Blood 2005 105: 3382-3384. [Full Text] [PDF] This article has been cited by other articles: S. J Lewis, D. A Lawlor, B. G Nordestgaard, A. Tybjaerg-Hansen, S. Ebrahim, J. Zacho, A. Ness, S. Leary, and G. D. Smith The methylenetetrahydrofolate reductase C677T genotype and the risk of obesity in three large population-based cohorts. Eur. J. Endocrinol., July 1, 2008; 159(1): 35 - 40. [Abstract] [Full Text] [PDF] W. Ageno, C. Becattini, T. Brighton, R. Selby, and P. W. Kamphuisen Cardiovascular Risk Factors and Venous Thromboembolism: A Meta-Analysis Circulation, January 1, 2008; 117(1): 93 - 102. [Abstract] [Full Text] [PDF] R. P. Agarwal, S. M. Peters, M. Shemirani, and N. von Ahsen Improved Real-Time Multiplex Polymerase Chain Reaction Detection of Methylenetetrahydrofolate Reductase (MTHFR) 677C>T and 1298A>C Polymorphisms Using Nearest Neighbor Model-Based Probe Design J. Mol. Diagn., July 1, 2007; 9(3): 345 - 350. [Abstract] [Full Text] [PDF] R. Y.L. Zee, S. Mora, S. Cheng, H. A. Erlich, K. Lindpaintner, N. Rifai, J. E. Buring, and P. M Ridker Homocysteine, 5,10-Methylenetetrahydrofolate Reductase 677C>T Polymorphism, Nutrient Intake, and Incident Cardiovascular Disease in 24 968 Initially Healthy Women Clin. Chem., May 1, 2007; 53(5): 845 - 851. [Abstract] [Full Text] [PDF] S. Kabukcu, N. Keskin, A. Keskin, and E. Atalay The Frequency of Factor V Leiden and Concomitance of Factor V Leiden With Prothrombin G20210A Mutation and Methylene Tetrahydrofolate Reductase C677T Gene Mutation in Healthy Population of Denizli, Aegean Region of Turkey Clinical and Applied Thrombosis/Hemostasis, April 1, 2007; 13(2): 166 - 171. [Abstract] [PDF] C. A. Boger, M. Stubanus, T. Haak, A. K. Gotz, J. Christ, U. Hoffmann, G. A. J. Riegger, B. K. Kramer, and for the GENDIAN Study Group Effect of MTHFR C677T genotype on survival in type 2 diabetes patients with end-stage diabetic nephropathy Nephrol. Dial. Transplant., January 1, 2007; 22(1): 154 - 162. [Abstract] [Full Text] [PDF] M. C. Reed, H. F. Nijhout, M. L. Neuhouser, J. F. Gregory III, B. Shane, S. J. James, A. Boynton, and C. M. Ulrich A Mathematical Model Gives Insights into Nutritional and Genetic Aspects of Folate-Mediated One-Carbon Metabolism J. Nutr., October 1, 2006; 136(10): 2653 - 2661. [Abstract] [Full Text] [PDF] A. M Devlin, R. Clarke, J. Birks, J. G. Evans, and C. H Halsted Interactions among polymorphisms in folate-metabolizing genes and serum total homocysteine concentrations in a healthy elderly population Am. J. Clinical Nutrition, March 1, 2006; 83(3): 708 - 713. [Abstract] [Full Text] [PDF] S. J Lewis, S. Ebrahim, and G. Davey Smith 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, November 5, 2005; 331(7524): 1053. [Abstract] [Full Text] [PDF] A. Tripodi, V. Chantarangkul, M. Menegatti, L. Tagliabue, and F. Peyvandi Performance of Clinical Laboratories for DNA Analyses to Detect Thrombophilia Mutations Clin. Chem., July 1, 2005; 51(7): 1310 - 1311. [Full Text] [PDF] T. Fahey, P. Brindle, and S. Ebrahim The polypill and cardiovascular disease BMJ, May 7, 2005; 330(7499): 1035 - 1036. [Full Text] [PDF] G. Davey Smith and S. Ebrahim What can mendelian randomisation tell us about modifiable behavioural and environmental exposures? BMJ, May 7, 2005; 330(7499): 1076 - 1079. [Full Text] [PDF] R. Marcucci, A. M. Gori, R. Abbate, J. Frederiksen, K. Juul, A. Tybjaerg-Hansen, and B. G. Nordestgaard Hyperhomocysteinemia: cause or effect of disease? 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