MTHFR mutation and carotid wall thickness in aging non diabetic women.

A mild hyperhomocysteinemia (Hey) has been recognized as cardiovascular risk factor in the general population. It may be due either to genetic or environmental factors. The genetic defect responsible for HCy has been identified in a mutation of the gene encoding for methylenetetrahydrofolate reductase (MTHFR). Several authors have observed an increased atherothrombotic risk in subjects homozygotes for the mutation. Few data are available concerning the relation between MTHFR gene mutation and the degree of involvement of carotid arteries. The aim of our study was to evaluate ifhomozygosis for MTHFR mutation was associated to an increased arterial wall thickness in a group of postmenopausal women without clinical history of CHD. We studied 99 non smokers women with a normal glucose tolerance after an OGGT. None of the women had any emodinamically significant carotid stenosis on the basis of a Duplex examination performed within the six months preeceding the enrollment. We evaluated BMI, lipid profile, plasma vitamine BI2 and folate levels, homocysteinemia, systolic and diastolic blood pressure values. A blood sample was collected for DNA extraction and MTHFR polymorphism determination by PCR technique. Moreover, all women underwent a Duplex color scanning with evaluation of the wall thickness. Mean BMI was 27.8+5.2 kg/m2. Plasma total cholesterol was 241.6+47.7 mg/dl, HDL-cholesterol was 52.3+10.6 mg/dl, LDL-cholesterol 152.2+62.4 mg/dl; plasma triglycerides was 103+40.2 mg/dL Plasma B12 median value was 268-I-89.5 pg/ml and plasma folate was 4.5+2.0 ng/ml. Mean plasma homoeysteine was 10.8+1.9 nmol/ml. Hypertension was present in 48% of the study group; all the hypertensive patients were on pharmacologic treatment. Systolic blood pressure was 134+16 mm Hg and diastolic was 81 +5 mm Hg. 21.21% of the population resulted homozygous for normal MTHFR gene polymorphism; 65.65% was heterozygous for the mutation and 13.13% was homozygous for the mutation. Dividing the population in two groups(homozygous for the mutation vs other people), there were no differences in anthropometric and biochemical parameters between the two groups. Median value of carotid wall thickness in the whole population was 0.11 mm (0.07- 0.6). By ANCOVA after correction for age, BMI, plasma lipid values, arterial hypertension, duration of hypertension, plasma B12 and folate, mean wall thickness was significantly higher in the subgroup of subjects homozygotes for mutation (0.26+0.042 vs 0.15 5: 0.015; p < 0.03). These data show that in postmenopausal non diabetic women a condition of homozygosis for the mutation of MTHFR gene, even in absence of significant stenosis, is associated to an increased carotid thickness, suggesting that MTHFR mutation could be a useful indicator of early atherosclerotic damage even in the general population.