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We examined the relationship between the 677C >T polymorphism in the MTHFR gene and tHcy in normotensive (NT) and hypertensive (HT) subjects and the influence of sex and age in a cross-sectional study. Smoking habits, history of vascular disease, diabetes, and tHcy were significantly associated with T allele as hypertension risk factors. The T allele was significantly related with higher tHcy in (i) men versus women (P < .01), (ii) men and women older than 47 years versus the younger ones (P < .05 and P < .001, respectively), (iii) HT women versus NT women (P < .01), and (iv) older HT women versus older NT women (P < .01). We found an association between the 677C>T MTHFR polymorphism and tHcy with hypertension that in women is manifested with age.

Homocysteine, a non-protein amino acid, important risk factor for atherosclerosis and thrombosis, causes dysfunction of vascular endothelial cells traduced in inadequate vasodilatation mechanism, is pro-inflammatory and induces endoplasmic reticulum stress. The more reactive conformation is the homocysteine thiolactone (HcyT), product to the nonspecific action of methionyl-tRNA synthetase, which is incorporated into proteins by disulfide bonds (S-homocysteinilation) or amide bonds (N-homocysteinilation) affecting protein structure and function leading to cell toxicity, autoimmune responses and atherogenesis. The enzyme paraoxonase-1 (PON1), part of high density lipoprotein (HDL), had been studied only for its ability to hydrolyze organophosphate derivatives. But, more recently it has been attributed other important role. The enzyme activities are involving in protecting against the development of atherosclerosis, by preventing oxidation of lipoproteins and hydrolyze HcyT. There is growing evidence about the protective role of PON1 in vascular disease. Genetic factors (polymorphisms of the PON1), environmental and lifestyle influence their concentration and biological activity, but drugs used as cardioprotectives and lipid-lowering or others, such as antibiotics and steroids, are also important modulators. This review is an updated of the most prominent information on clinical and experimental studies for understanding the role of the PON-1 in the protection against development of atherosclerosis.