Effect of methylenetetrahydrofolate reductase gene mutation on plasma homocysteine level and its prevalence in arterial diseases

Two common polymorphisms of the methylenetetrahydrofolate reductase [MTHFR] gene, the thermolabile C677T and A1298C polymorphism may contribute to hyperhomocysteinemia, a known risk factor for vascular diseases. Twenty with coronary artery disease [CAD] and 20 patients with cerebro-vascular stroke [CVS] were compared with 20 controls. Using PCR and restriction fragment length polymorphism [RFLP] analysis, we studied C677T and A 1298C MTHFR genotypes and their combined effect on homocysteine, measured by chemiluminescent enzymatic immunometric assay. Homocysteine values were significantly higher in CAD [16.12 +/- 5.09 micromol/L] and in CVS [16.79 +/- 5.93 micromol/L] compared with controls [10.43 +/- 2.57 micromol/L, P<0.01]. In C677T genotype, homocysteine was significantly higher in TT [18.26 +/- 2.75 micromol/L] and in CT [17.60 +/- 7.22 micromol/L] than in CC genotype [12.94 +/- 4.16 micromol/L, P<0.01]. However, in A1298C genotype, no significant difference was found between the mean homocysteine level in AA genotype [14.14 +/- 4.32 micromol/L], AC genotype [14.25 +/- 5.50 micromol/L] and CC genotype patients [16.28 +/- 8.76 micromol/L, P>0.05]. A significant positive correlation between plasma homocysteine and cholesterol [r=0.37, P<0.01] and LDL-C levels was found [r=0.321, P<0.05]. The percentage of patients with high homocysteine level [>/-15 micromol/L] were significantly higher in CAD [50%] and CVS [55%] than controls [5%, P<0.01, odd ratio=21]. In contrast to the A1298C polymorphism, the MTHFR TT and CT genotypes were associated with hyperhomocysteinemia. The knowledge of the MTHFR mutation [C677T] status might represent a way to identify subjects at high risk for hyperhomocysteinemia