ABSTRACT
Title
Clinical implications of MTHFR C677T polymorphism in cardiovascular diseases
Authors
S. Magi1,2, P. Castaldo1,2, G.P. Perna3, M. Marini3, M. Francioni3, A.A. Nasti1, G. Galeazzi1, C.A. Violet1, S. Amoroso1,2
1Section of Pharmacology, Department of Neuroscience, University “Politecnica delle Marche”, Ancona, Italy; 2Division of Clinical Pharmacology and 3Cardiology G.M. Lancisi, “Azienda Ospedaliero-Universitaria Ospedali Riuniti”, Ancona, Italy.
1Section of Pharmacology, Department of Neuroscience, University “Politecnica delle Marche”, Ancona, Italy; 2Division of Clinical Pharmacology and 3Cardiology G.M. Lancisi, “Azienda Ospedaliero-Universitaria Ospedali Riuniti”, Ancona, Italy.
Abstract
The enzyme 5, 10-methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the folate pathway since it catalyzes the irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which serves as a methyl donor in the remethylation of homocysteine (Hcy) to methionine. Elevated Hcy blood levels have been shown to increase the risk for (1) atherosclerosis, which could eventually result in a heart attack and/or stroke, and (2) for venous thrombosis. People may have high Hcy levels for several reasons including deficiency of B vitamins and folate in their diets; but high Hcy levels have been also found in patients with kidney disease, low levels of thyroid hormones, psoriasis and in people taking certain medications (such as antiepileptic drug and methotrexate). It has been shown that in some people high Hyc levels can result from genetic disturbances, in particular the C677T substitution in the gene coding for the MTHFR enzyme. This polymorphism impairs the MTHFR ability to process folate, leading to elevated levels of Hyc, however its clinical importance remains to be established.
The aim of the present study was to evaluate a possible correlation between the MTHFR C677T mutation and the incidence of cardiovascular diseases in patients without any other conventional risk factors, in particular in the absence of high Hyc levels.
We sought for the presence of the MTHFR C677T mutation by sequencing the genomic DNA from patients with cardiovascular diseases in the absence of conventional risk factors. Preliminary results showed that those patients who developed serious cardiovascular diseases carried mainly a heterozygous (677CT) or homozygous (677TT) genotype for the MTHFR C677T mutation. By contrast, control group (patients without serious cardiovascular diseases and/or conventional risk factors) carried mostly a homozygous (677CC) genotype.
In conclusion, our results suggest that the presence of the MTHFR C677T mutation may represent a valuable risk factor (in absence of any others) in patients with serious cardiovascular diseases and its identification may address the clinician in choosing the appropriate therapy.
The aim of the present study was to evaluate a possible correlation between the MTHFR C677T mutation and the incidence of cardiovascular diseases in patients without any other conventional risk factors, in particular in the absence of high Hyc levels.
We sought for the presence of the MTHFR C677T mutation by sequencing the genomic DNA from patients with cardiovascular diseases in the absence of conventional risk factors. Preliminary results showed that those patients who developed serious cardiovascular diseases carried mainly a heterozygous (677CT) or homozygous (677TT) genotype for the MTHFR C677T mutation. By contrast, control group (patients without serious cardiovascular diseases and/or conventional risk factors) carried mostly a homozygous (677CC) genotype.
In conclusion, our results suggest that the presence of the MTHFR C677T mutation may represent a valuable risk factor (in absence of any others) in patients with serious cardiovascular diseases and its identification may address the clinician in choosing the appropriate therapy.