title: Genetic polymorphisms involved in folate metabolism and concentrations of methylmalonic acid and folate on plasma homocysteine and risk of coronary artery disease.
abstract: OBJECTIVE
  Alterations in the enzymes involved in homocysteine (Hcy) metabolism or vitamin deficiency could play a role in coronary artery disease (CAD) development. This study investigated the influence of MTHFR and MTR gene polymorphisms, plasma folate and MMA on Hcy concentrations and CAD development. MMA and folate concentrations were also investigated according to the polymorphisms.
  
  
  METHODS
  Two hundred and eighty-three unrelated Caucasian individuals undergoing coronary angiography (175 with CAD and 108 non-CAD) were assessed in a case-control study. Plasma Hcy and MMA were measured by liquid chromatography/tandem mass spectrometry. Plasma folate was measured by competitive immunoassay. Dietary intake was evaluated using a nutritional questionnaire. Polymorphisms MTHFR and MTR were investigated by polymerase chain reaction (PCR) followed by enzyme digestion or allele-specific PCR.
  
  
  RESULTS
  Hcy mean concentrations were higher in CAD patients compared to controls, but below statistical significance (P = 0.246). Increased MMA mean concentrations were frequently observed in the CAD group (P = 0.048). Individuals with MMA concentrations >0.5 micromol/l (vitamin B(12) deficiency) were found only in the CAD group (P = 0.004). A positive correlation between MMA and Hcy mean concentrations was observed in both groups, CAD (P = 0.001) and non-CAD (P = 0.020). MMA mean concentrations were significantly higher in patients with hyperhomocysteinemia in both groups, CAD and non-CAD (P = 0.0063 and P = 0.013, respectively). Folate mean concentration was significantly lower in carriers of the wild-type MTHFR 1298AA genotype (P = 0.010).
  
  
  CONCLUSIONS
  Our results suggest a correlation between the MTHFR A1298C polymorphism and plasma folate concentration. Vitamin B(12) deficiency, reflected by increased MMA concentration, is an important risk factor for the development both of hyperhomocysteinemia and CAD.
authors.affiliation: Genetics and Molecular Biology Research Unit-UPGEM, São José do Rio Preto Medical School-FAMERP, Av. Brigadeiro Faria Lima, N masculine 5416, Bloco U-6, São José do Rio Preto, SP, 15.090-000, Brazil. patriciabiselli@famerp.br
authors.forename: Patrícia Matos
authors.initials: PM
authors.lastname: Biselli
authors.forename: Alexandre Rodrigues
authors.initials: AR
authors.lastname: Guerzoni
authors.forename: Moacir Fernandes
authors.initials: MF
authors.lastname: de Godoy
authors.forename: Marcos Nogueira
authors.initials: MN
authors.lastname: Eberlin
authors.forename: Renato
authors.initials: R
authors.lastname: Haddad
authors.forename: Valdemir Melechco
authors.initials: VM
authors.lastname: Carvalho
authors.forename: Hélio
authors.initials: H
authors.lastname: Vannucchi
authors.forename: Erika Cristina
authors.initials: EC
authors.lastname: Pavarino-Bertelli
authors.forename: Eny Maria
authors.initials: EM
authors.lastname: Goloni-Bertollo
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008764:Methylmalonic Acid / Q000097:blood*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D006710:Homocysteine; D008764:Methylmalonic Acid; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase