| Objective: A common mutation, C677T, in the methylenetetrahydrofolate reductase (MTHFR) gene results in elevating homocysteine (Hcy) levels, and presumably, in increasing atherosclerotic risk. We conducted a case-control study to investigate the relationship between the MTHFR gene C677T mutation with hyperhomocysteinemia and Coronary Artery Disease (CAD) in the northern Chinese population. In addition, the oxidative stress in hyperhomocysteinemia was also observed.Methods: The diagnoses of CAD of all the studied subjects were confirmed by coronary angiography. Eighty-one CAD patients and seventy-two non-CAD ones were recruited in the study. PCR-PFLC was used for genotyping. Plasma folate concentration was measured by radioimmunologic assay and plasma Hcy by High performance liquid chromatography (HPLC). And some patients were divided into two groups according to their plasma Hey concentrations by the standard of 15umol/l. One is hyperhomocysteinemia patients group (49), the other is normal ones (70). Plasma malondialdehyde (MDA) and superoxide dismutase (SOD) were measured-by standard protocols.Results:1 Plasma homocysteine concentrations were significantly higher in CAD patients as compared to non-CAD ones (16.76±1.31umol/l vs. 12.6±1.01umol/l,P<0.05). However, there was no significant difference in folate levels between the two groups (7.16±0.38ng/ml vs. 7.34±0.64 ng/ml, P>0.05).2 Allele and genotype frequencies among CAD patients and non-CAD subjects were compatible with Hardy-Weinberg equilibrium. In the CAD group, genotype TT was not significantly more frequent than that in the non-CAD group (17.3% vs. 13.8% in genotypes, P>0.05).3 Plasma homocysteine concentrations were significantly higher in the genotype TT (24.08 ±1.18 umol/1) than that in genotype CT (15.69 ±1.19 umol/1) and genotype CC (11.71 ±1.29 umol/1) in CAD patients (P<0.01).4 Plasma folate levels were lower in the genotype TT than that in genotype CT and that in genotype CC in CAD patients, but no statistical differentence was found (P>0.05).5 Plasma Hcy concentrations had significant non-linear inverse correlation with plasma folate concentrations in the mutation homozygotes (TT) in CAD patients (P<0.05).6 Plasma MDA was significantly higher in the hyperhomocysteinemia patients than that in controls (3.78±0.41 umol/1 vs. 2.67 ±0.21 umol/1, P<0.01). Plasma SOD levels were not statistically different between the two groups (63.23 ± 4.26 umol/1 vs. 66.67 ±6.51 umol/1, P>0.05).Conclusion:1 The plasma homocysteine concentration was much higher in CAD patients than that in non-CAD ones, which implied that hyperhomocysteinemia might be one of the risk factors of CAD in this group of northern Chinese population;2 The plasma homocysteine concentration was higher in MTHFR TTgenotype, but there was no significant difference in the TT genotype distribution between CAD patients and non-CAD ones. Therefore, MTHFR TT genotype could not be settled as an independ risk factor for CAD in this group of northern Chinese population;3 The plasma MDA concentration was higher in hyperhomocysteinemia patients, implying that hyperhomocysteinemia could induce oxidative stress, which might be one of the mechanisms in vascular damage.
|
PDF Full Text Request