title: Homocysteine and the MTHFR 677C-->T allele in premature coronary artery disease. Case control and family studies.
abstract: BACKGROUND
  The aim of this work was to evaluate the role of homocysteine, and the MTHFR 677C-->T allele as risk factors for premature coronary artery disease and to analyse the inheritance of this metabolic disorder.
  
  
  METHODS
  Case-control and family studies were performed in a sample of 76 male patients (age < 55), 95 age-matched controls and 89 patients' offspring. Plasma total homocysteine concentrations, its nutritional determinants and the frequency of the MTHFR 677C-->T allele were measured, in addition to conventional risk factors.
  
  
  RESULTS
  Mild hyperhomocysteinemia (above the 90th percentile of the control group) was seen in 22.4% of patients (P = 0.02) and was an independent predictor of premature coronary artery disease (odds ratio of 3.2). The frequencies of the 677T allele in patients and controls were 0.37 and 0.36 and those of the TT genotype were 0.15 and 0.14, respectively. Homozygosity for the 677T allele was associated with significantly higher homocysteine values (P < 0.00001). Among TT patients, 64% had mild hyperhomocysteinemia, as compared to 23% of TT controls. Mild hyperhomocysteinemia showed a strong hereditary component, as 36% of patients' offspring had homocysteine levels above the age-adjusted 90th percentile compared to only 13% of patients' spouses. Among children with the TT genotype, the proportion raised to 83% (P < 0.001).
  
  
  CONCLUSIONS
  In this Spanish population, mild hyperhomocysteinemia is associated with the risk of premature coronary artery disease and is highly prevalent in offspring of patients with this condition. The MTHFR TT genotype is associated with hyperhomocysteinemia, but not with coronary artery disease.
authors.affiliation: Servei de Medicina Interna, Hospital de Bellvitge, L'Hospitalet de Llobregat, Spain. xpinto@csub.scs.es
authors.forename: X
authors.initials: X
authors.lastname: Pintó
authors.forename: M A
authors.initials: MA
authors.lastname: Vilaseca
authors.forename: N
authors.initials: N
authors.lastname: Garcia-Giralt
authors.forename: I
authors.initials: I
authors.lastname: Ferrer
authors.forename: M
authors.initials: M
authors.lastname: Palá
authors.forename: J F
authors.initials: JF
authors.lastname: Meco
authors.forename: C
authors.initials: C
authors.lastname: Mainou
authors.forename: J M
authors.initials: JM
authors.lastname: Ordovás
authors.forename: D
authors.initials: D
authors.lastname: Grinberg
authors.forename: S
authors.initials: S
authors.lastname: Balcells
mesh_terms: D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D003327:Coronary Disease / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005192:Family Health; D005787:Gene Frequency; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D016015:Logistic Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D017354:Point Mutation; D012307:Risk Factors
chemical_list: D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)