title: The methylenetetrahydrofolate reductase C677T gene mutation is associated with hyperhomocysteinemia, cardiovascular disease and plasma B-type natriuretic peptide levels in Korea.
abstract: BACKGROUND
  Hyperhomocysteinemia is known to be a risk factor for cardiovascular diseases and is associated with a common mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (677 C>T). The aims of this study were to confirm: 1) the association between the MTHFR C677T mutation and plasma homocysteine (Hcy) levels; 2) the MTHFR C677T mutation as a risk factor; 3) the association of the MTHFR C677T mutation and plasma B-type natriuretic peptide (BNP) levels; and 4) the correlation between Hcy and BNP levels in cardiovascular diseases.
  
  
  METHODS
  A total of 227 patients for whom BNP was measured were enrolled in this study. Laboratory parameters included BNP, creatine kinase (CK), the myocardial isoenzyme of CK (CK-MB), troponin I (TnI), Hcy, C-reactive protein (CRP), lactate dehydrogenase (LDH), creatinine and folate. The MTHFR genotype was evaluated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was shown by an electrophoretic technique.
  
  
  RESULTS
  The prevalence of TT homozygotes was significantly higher in patients with cardiovascular diseases than in patients without cardiovascular diseases (p=0.0001). Patients homozygous for the TT mutation had the highest plasma Hcy levels compared with wild-type CC homozygotes and CT mutant heterozygotes (p=0.0001). Plasma BNP concentrations were significantly higher in patients with MTHFR C677T mutation compared to patients without the mutation (p<0.05). Plasma BNP concentrations were positively correlated with Hcy concentrations (r=0.196, p<0.001). Multivariate logistic regression analysis showed that elevated concentrations of BNP, CRP, Hcy and the presence of the MTHFR C677T mutation independently contributed to the prediction of cardiovascular diseases.
  
  
  CONCLUSIONS
  In cardiovascular diseases, the MTHFR C677T mutation: 1) is associated with plasma Hcy levels; 2) is an independent risk factor for cardiovascular diseases, 3) is associated with plasma BNP levels, and 4) plasma Hcy levels are positively correlated with plasma BNP levels.
authors.affiliation: Department of Laboratory Medicine, Ewha Womans University, College of Medicine, Seoul, Korea.
authors.forename: Sung Eun
authors.initials: SE
authors.lastname: Cho
authors.forename: Ki Sook
authors.initials: KS
authors.lastname: Hong
authors.forename: Gil Ja
authors.initials: GJ
authors.lastname: Shin
authors.forename: Wha Soon
authors.initials: WS
authors.lastname: Chung
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics*; D003402:Creatine Kinase / Q000097:blood; D003404:Creatinine / Q000097:blood; D005260:Female; D005492:Folic Acid / Q000097:blood; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000209:etiology / Q000235:genetics*; D007527:Isoenzymes / Q000097:blood; D007723:Korea; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D020097:Natriuretic Peptide, Brain; D019210:Troponin I / Q000097:blood
chemical_list: D015415:Biomarkers; D007527:Isoenzymes; D019210:Troponin I; D006710:Homocysteine; D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein; D005492:Folic Acid; D003404:Creatinine; D007770:L-Lactate Dehydrogenase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D003402:Creatine Kinase