ABSTRACT
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
ABSTRACT
Accelerated arterial stiffness has been linked in diabetes to hyperglycaemia, hyperinsulinaemia, and impaired glucose tolerance. In this work, we studied two groups: Normotensive diabetic patients Group [A] and non diabetic age and gender matched controls group Group [B]. We excluded those with hypertension, hypercholesterolemia, smokers or ex-smokers and patients with history of or complaining of peripheral vascular disease or coronary artery disease. The aim of work was to study the relationship between arterial compliance and diabetic status in normotensive diabetic patients. The two groups [A and B] were compared as regards the clinical data, laboratory investigations, echocardiographic studies, carotid duplex evaluation [intima-media thickness and incidence of atherosclerotic plaques], pulse wave velocity measurements. On comparing both groups we found that diabetic patients had average pulse wave velocity, higher incidence of diastolic dysfunction and had lower fractional shortening values and E/A ratio on echocardiographic evaluation. Correlation of glycosylated haemoglobin with the other study parameters showed a significantly positive correlation with pulse wave velocity [PWV] among the whole population and with mean intima-media thickness [Mean IMT] among the whole population and in diabetics. Correlation of pulse wave velocity with the study parameters revealed a statistically significant positive correlation with mean-intima media thickness among the total population as well as in diabetics. In this study we concluded that early vascular damage and arterial stiffness is independently related to glycaemic status in diabetic patients even before evident clinical manifestations of macrovascular affection such as hypertension, increase in intima-media thickness, development of atherosclerotic plaques, symptoms or signs of peripheral vascular disease or coronary artery disease. We don't know if tight glycaemic control could reverse these early changes of vascular compliance or not and that needs further investigation. Pulse wave velocity is a non invasive, inexpensive and feasible method for early detection of vascular damage and impaired arterial function, so that therapeutic interventions can be evaluated, in order to reduce future cardiovascular complications and thereby increase both duration and quality of life.