Thrombosis and risk factors: A comment

Abstract

We read with great interest the recent publication by Akar related to thrombosis and risk factors, in which he reached in conclusion that in case of need only homocysteine (Hcy) levels should be routinely analyzed and not the 5, 10-methylenetetrahydrofolate reductase (mTHFr) 677 T polymorphism [1]. The methylation of Hcy to methionine is catalyzed by the mTHFr enzyme. As far as is known, genetic deficiency of mTHFr is one cause leading to increased plasma Hcy levels [2]. But, it should not be forgotten that Hcy rises in many acquired and genetic conditions (Table) [3]. There are three main indications for determining plasma total Hcy: (a) to diagnose homocystinuria; (b) to identify individuals with or at risk of developing cobalamin or folate deficiency; (c) to assess total Hcy as a risk factor for cardiovascular and other disorders [4]. There is an involved question in this point: Is increased plasma total Hcy level related to both venous and arterial occlusive disease? And, if is it true, are polymorphism and mutation of mTHFr directly playing a role to augment the level of Hcy for cardiovascular disease (CvD)? As reviewed elsewhere, moderately increased plasma Hcy is associated with venous and arterial occlusion [5]. moreover, as it is known, the presence of mTHFr 677C→T polymorphism is a strong risk factor for increased plasma Hcy level but not for CvD [4]. In a metaanalysis including 11.162 CvD cases and 12.758 controls, with high Hcy levels in a state of low folate levels, the TT genotype was associated with a 16% increase in coronary heart disease risk [6]. Concordantly, previous studies had shown that the mTHFr 677C→T polymorphism is only associated with high Hcy levels or increased CvD risk in a setting of low folate status [6]. Hence, at higher dietary intakes of folate, the effect of the mTHFr 677C→T genotype has no adverse effect on plasma Hcy levels or on subsequent risk of CvD. The results support the hypothesis that impaired folate metabolism, resulting in high Hcy concentrations, plays a causal role in the occurrence of CvD. In view of cost effectiveness, do not investigate routinely mTHFr 677C→T polymorphism in the general or CvD population seems to be reasonable, but the other mutations of mTHFr could be still influential for high plasma Hcy levels.