Methylenetetrahydrofolate reductase polymorphism (C-677T) and coronary artery disease

1. Many studies have shown that hyperhomocysteinaemia is a risk factor for atherosclerotic vascular disease. A mutation (C-677T) in the gene coding for the methylenetetrahydrofolate reductase (MTHFR) enzyme has been shown to produce a thermolabile form of the enzyme. Homozygosity for this mutation has been correlated with an elevated plasma homocysteine concentration. The present study ai med to determine whether this mutation was a risk factor for coronary artery disease (CAD). This was achieved by comparing the frequency of the C-677T mutation in patients with angiographically proven CAD against angiographically normal patients in two separate U.K. samples. The analysis was repeated with CAD patients split into those with greater than or equal to 99% stenosis of arteries and those without, to establish whether the C-677T mutation could be correlated with severity of CAD. 2. Two patient groups were selected from London and Sheffield. The London group comprised 174 cases and 148 controls. The Sheffield group comprised 93 cases and 85 controls. The DNA samples of the patients were genotyped by polymerase chain reaction and restriction enzyme digestion. 3. For London the homozygous C-677T frequencies were: 0.07 (controls), 0.09 (CAD without greater than or equal to 99% stenosis) and 0.10 (CAD with greater than or equal to 99% stenosis). For Sheffield the homozygous C-677T frequencies were: 0.08 (controls), 0.10 (CAD without greater than or equal to 99% stenosis) and 0.11 (CAD with greater than or equal to 99 % stenosis). No association was found between the C-677T mutation and CAD in our sam pie geographical groups. Statistical comparison by genotype distribution for 0 VD (no vessel disease, i.e. 0% diameter reduction in all epicardial arteries) versus CAD without greater than or equal to 99% stenosis: London, P = 0.19; Sheffield, P = 0.53;0 VD versus CAD with greater than or equal to 99% stenosis: London, P = 0.23; Sheffield, P = 0.55.