title: The association between plasma homocysteine and coronary heart disease is modified by the MTHFR 677C>T polymorphism.
abstract: OBJECTIVE
  An elevated level of total plasma homocysteine (tHcy) has been associated with risk of coronary heart disease (CHD). The level of tHcy is affected by lifestyle, in addition to genetic predisposition. The methylene tetrahydrofolate reductase (MTHFR) 677C>T polymorphism (rs1801133) is among the strongest genetic predictors of tHcy. We examined whether the association between tHcy and CHD is modified by the MTHFR 677C>T polymorphism.
  
  
  METHODS
  Data from two case-control studies of first-time myocardial infarction (MI), Stockholm Heart Epidemiology Programme (SHEEP), and for MI and unstable angina, INTERGENE, were analysed in parallel.
  
  
  METHODS
  THcy was determined in a total of 1150 cases and 1753 controls.
  
  
  METHODS
  None.
  
  
  METHODS
  The outcome comprised first-time MI and unstable angina, subsumed as CHD. Logistic regression was used to investigate the association between tHcy and CHD, and its modification by genotype.
  
  
  RESULTS
  High tHcy was confirmed to be a risk factor for CHD in both studies. In SHEEP, the association between tHcy and MI was observed in MTHFR 677 C-homozygotes (OR=1.4, 95% CI 1.2 to 1.6, for a difference by 1 SD of log tHcy) and in heterozygotes (OR=1.3, 95% CI 1.1 to 1.6) but not in T-homozygotes, independent of smoking, physical activity and obesity. An effect modification of similar magnitude was observed but not statistically significant in the smaller INTERGENE study, and confirmed in a meta-analysis of both studies.
  
  
  CONCLUSIONS
  Two Swedish case-control studies showed that the association between elevated tHcy and CHD was confined to carriers of the MTHFR 677 C-allele, which could have implications for the efficiency of tHcy-lowering treatment.
authors.affiliation: Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, , Gothenburg, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Mehlig
authors.forename: K
authors.initials: K
authors.lastname: Leander
authors.forename: U
authors.initials: U
authors.lastname: de Faire
authors.forename: F
authors.initials: F
authors.lastname: Nyberg
authors.forename: C
authors.initials: C
authors.lastname: Berg
authors.forename: A
authors.initials: A
authors.lastname: Rosengren
authors.forename: L
authors.initials: L
authors.lastname: Björck
authors.forename: H
authors.initials: H
authors.lastname: Zetterberg
authors.forename: K
authors.initials: K
authors.lastname: Blennow
authors.forename: G
authors.initials: G
authors.lastname: Tognon
authors.forename: K
authors.initials: K
authors.lastname: Torén
authors.forename: E
authors.initials: E
authors.lastname: Strandhagen
authors.forename: L
authors.initials: L
authors.lastname: Lissner
authors.forename: D
authors.initials: D
authors.lastname: Thelle
mesh_terms: D000368:Aged; D000789:Angina, Unstable / Q000097:blood / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003327:Coronary Disease / Q000097:blood / Q000235:genetics*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D006710:Homocysteine; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: Myocardial Ischaemia And Infarction (IHD)