MUTATION C677T OF METHYLENETETRAHYDROFOLATE REDUCTASE GENE IS NOT ASSOCIATED WITH CORONARY-ARTERY DISEASE, BUT POSSIBLY WITH ALBUMINURIA, IN TYPE-2 DIABETIC-PATIENTS

The missense mutation in the 677th nucleotide (C677T) of methylenetetr ahydrofolate reductase gene causes substitution of valine (V) for alan ine (A) resulting in three genotypes VV,VA and AA. The VV genotype cau ses hyperhomocysteinemia and may be a risk factor for coronary artery disease. We determined genotypes by polymerase chain reaction and subs equent restriction fragment length analysis and compared them in 84 pa tients with type 2 diabetes and in 115 non-diabetic subjects with and without coronary disease. Fractional urinary excretion rate of albumin was assessed by nephelometry. The VV VA, and AA frequencies in the di abetic and in the control groups were 0.095, 0.357, 0.548 and 0.061, 0 .417, 0.522, respectively (p = NS, diabetic vs. controls, chi(2) test) . Genotype frequencies did not differ in either diabetic or control su bjects between those with or those without coronary disease (chi(2) te st). The fractional urinary excretion rate of albumin (mean +/-SD) in diabetic patients with the VV genotype i.e. 1.59 +/- 0.71 was lower (K ruskall-Wallis test p = 0.002) than in the other genotypes i.e. VA 5.9 8 +/- 9.75 and AA 3.75 +/- 4.77, respectively (post-hoc Mann-Whitney t est VV vs. VA p = 0.005 and VV vs. AA p 0.054, respectively). We found that in patients with type 2 diabetes the methylenetetrahydrofolate r eductase VV genotype was associated with a low urinary albumin excreti on but not with coronary artery disease or diabetes per se.