Genetic polymorphisms involved in folate metabolism and concentrations of methylmalonic acid and folate on plasma homocysteine and risk of coronary artery disease

• Published in: Journal of thrombosis and thrombolysis Vol. 29; no. 1; pp. 32 - 40
• Main Authors: Biselli, Patrícia Matos, Guerzoni, Alexandre Rodrigues, de Godoy, Moacir Fernandes, Eberlin, Marcos Nogueira, Haddad, Renato, Carvalho, Valdemir Melechco, Vannucchi, Hélio, Pavarino-Bertelli, Érika Cristina, Goloni-Bertollo, Eny Maria
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-01-2010; Springer Nature B.V
• Subjects: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics; Adult; Aged; Cardiology; Case-Control Studies; Coronary Artery Disease - enzymology; Coronary Artery Disease - genetics; Female; Folic Acid - blood; Hematology; Homocysteine - blood; Humans; Male; Medicine; Medicine & Public Health; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Methylmalonic Acid - blood; Middle Aged; Polymorphism, Genetic; Risk Factors; Methylmalonic acid; Homocysteine; Coronary artery disease; Genetic polymorphisms
• ISSN: 0929-5305; 1573-742X
• DOI: 10.1007/s11239-009-0321-7

Objectives
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 μmol/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).
Conclusion
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.