title: Red blood cell methylfolate and plasma homocysteine as risk factors for venous thromboembolism: a matched case-control study.
abstract: BACKGROUND
  Moderate hyperhomocysteinaemia is a risk factor for venous thromboembolism. We do not know whether this risk depends on homocysteine itself or on components of the homocysteine remethylation pathway, such as methylfolate. We did a case-control study to analyse the relation between the major components of the homocysteine remethylation pathway and risk of venous thromboembolism.
  
  
  METHODS
  We measured concentrations of homocysteine, methionine, and folate in plasma, total folate and methylfolate in red-blood cells, and 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T genotype and other known risk factors for venous thromboembolic disease in 243 patients with deep vein thrombosis or pulmonary embolism and controls matched for sex and age.
  
  
  RESULTS
  Concentrations in plasma of homocysteine differed significantly between cases and controls. We noted a strong concentration-dependent association between concentrations of methylfolate in red-blood cells and risk of venous thromboembolism. The adjusted conditional odds ratio ranged from 1.0 for methylfolate 249 microg/L or greater to 7.1 (3.2-15.8) for methylfolate 141 microg/L or less. Methionine concentrations below the median were also independently associated with raised risk of venous thromboembolic disease, as were established risk factors such as high body-mass index, history of cancer, family history of thromboembolism, oral contraceptive use, and factor V Leiden mutation. Furthermore, the association between concentrations of methylfolate in red-blood cells and risk of thromboembolism varied according to MTHFR C677T genotype.
  
  
  CONCLUSIONS
  Measurement of methylfolate concentrations in red-blood cells might help to identify people at risk of venous thromboembolism.
authors.affiliation: Internal Medicine Department University Hospital Saint Eloi, Montpellier, France. i-quere@chu-montpellier.fr
authors.forename: Isabelle
authors.initials: I
authors.lastname: Quéré
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Perneger
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Zittoun
authors.forename: Hélène
authors.initials: H
authors.lastname: Bellet
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Gris
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Daurès
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Schved
authors.forename: Eric
authors.initials: E
authors.lastname: Mercier
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Laroche
authors.forename: Michel
authors.initials: M
authors.lastname: Dauzat
authors.forename: Henri
authors.initials: H
authors.lastname: Bounameaux
authors.forename: Charles
authors.initials: C
authors.lastname: Janbon
authors.forename: Philippe
authors.initials: P
authors.lastname: de Moerloose
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000097:blood / Q000235:genetics; D011655:Pulmonary Embolism / Q000097:blood* / Q000235:genetics; D012307:Risk Factors; D013763:Tetrahydrofolates / Q000097:blood*; D020246:Venous Thrombosis / Q000097:blood* / Q000235:genetics
chemical_list: D013763:Tetrahydrofolates; D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C005984:5-methyltetrahydrofolate