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 μmol/L) and in CVS (16.79 ± 5.93 μmol/L) compared with controls (10.43 ± 2.57 μmol/L, P < 0.01). In C677T genotype, homocysteine was significantly higher in TT (18.26 ± 2.75 μmol/L) and in CT (17.60 ± 7.22 μmol/L) than in CC genotype (12.94 ± 4.16 μmol/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 μmol/L), AC genotype (14.25 ± 5.50 μmol/L) and CC genotype patients (16.28 ± 8.76 μmol/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 μmol/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.