title: The C677T mutation in methylenetetrahydrofolate reductase gene, plasma homocysteine concentration and the risk of coronary artery disease.
abstract: BACKGROUND
  The C677T mutation in methylenetetrahydrofolate reductase (MTHFR) gene is one of the causes of an elevated homocysteine plasma concentration and is probably one of the atherosclerotic risk factors.
  
  
  OBJECTIVE
  To assess the relationship between the presence of the MTHFR gene mutation, plasma homocysteine concentration and the risk of coronary artery disease (CAD).
  
  
  METHODS
  The study group consisted of 120 consecutive patients (78% were male, mean age 59.2+/-9.6 years) with angiographically confirmed CAD and 106 healthy volunteers (76% were male, mean age 47.4+ or -6.0 years). The MTHFR gene mutation was detected based on the polymerase chain reaction and digestion with restrictive endonuclease HinfI. Total homocysteine plasma concentration was measured using HPLC. Folic acid and vitamin B12 plasma levels were assessed using the chemiluminescence method. Hyperhomocysteinemia was defined as homocysteine concentration > or =90 percentile of the control group which was > or =12.4 micro mol/L.
  
  
  RESULTS
  The incidence of the mutation of allele T and the genotype TT was similar in patients and controls (51.7% vs 56.6%, and 9.2% vs 10.4%, NS, respectively). The folic acid and vitamin B12 levels were not related to the MTHFR genotype (folic acid: 8.1 ng/L in homozygotes TT vs 8.6 in heterozygotes CT and 8.3 in homozygotes CC; and vitamin B12: 273 pg/L vs 303.3 vs 314.3, respectively). Although homozygotes TT had significantly higher homocysteine concentration than heterozygotes and homozygotes CT or CC (15.4 vs 11.0 vs 11.2 micro mol/L, p<0.001), the odds ratio for CAD in genotype TT was 0.87 (95% CI 0.5-2.1, NS). The odds ratio in subjects with at least one mutated T allele was 0.82 (95%CI 0.5-1.4, NS). Homocysteine plasma concentration was significantly higher in patients with CAD than controls (12.8+/-5.1 vs 10.0+/-5.0 micro mol/L, p<0.001) and correlated significantly with folic acid (r= -0.28, p=0.0001), vitamin B12 (r= -0.19, p<0.005), age (r=0.35, p=0.0001) and creatinine (r=0.26, p=0.0001). The odds ratio for CAD in subjects with hyperhomocysteinemia was 7.1 (95%CI 3.4-14.9, p=0.001) and was 2.6 (95%CI 1.6-4.1, p=0.0001) with a homocysteine increase of 5 micro mol/L. Multivariate analysis showed that hyperhomocysteinemia was an independent risk factor of CAD (OR 2.7, 95%CI 1-7.2, p<0.05). Conclusions. Hyperhomocysteinemia rather than a mutation in the methylenetetrahydrofolate reductase gene, is an independent risk factor of coronary artery disease.
authors.affiliation: 1st Department of Coronary Artery Disease, National Institute of Cardiology, Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Kadziela
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Janas
authors.forename: Zofia
authors.initials: Z
authors.lastname: Dzielińska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Szperl
authors.forename: Danuta
authors.initials: D
authors.lastname: Gaździk
authors.forename: Ewa
authors.initials: E
authors.lastname: Chotkowska
authors.forename: Walerian
authors.initials: W
authors.lastname: Piotrowski
authors.forename: Witold
authors.initials: W
authors.lastname: Ruzyłło
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000201:enzymology / Q000235:genetics; D003545:Cysteine / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013912:Threonine / Q000235:genetics; D014805:Vitamin B 12 / Q000097:blood
chemical_list: D006710:Homocysteine; D013912:Threonine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D003545:Cysteine; D014805:Vitamin B 12