Methylene tetrahydrofolate reductase gene and coronary artery disease

Hyperhomocysteinemia has been identified as a risk factor for coronary artery disease (CAD). 1-9 In a nested case control study in Norway on 21,826 subjects in general population, hyperhomocysteinemia was clearly identified as an independent risk factor for CAD with no threshold level. 9 Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the methylation of homocysteine and its role in this pathway is outlined in Figure. Several inherited enzyme defects that can lead to elevated level of plasma homocysteine have been reported. Defective cystathionine b-synthase was the first to be extensively studied. 10 However, defective remethylation of homocysteine due to defective MTHFR was another cause of hyperhomocysteinemia leading to premature vascular disease. 11