Review paper
Methylenetetrahydrofolate reductase polymorphisms as possible risk factors of venous thrombosis – too weak to take care, too frequent to be ignored…

Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in the metabolism of homocysteine. It has been found that an increased concentration of homocysteine in circulating blood (hyperhomocysteinaemia) may lead to blood vessel damage, which may further be associated with higher risk of various cardiovascular disorders, including venous thrombosis (VT). Among various factors identified to be responsible for hyperhomocysteinaemia, an important role is played by the genetically determined decrease of MTHFR enzymatic activity. This decrease may result from several nucleotide polymorphisms (SNPs) of the gene encoding for MTHFR, with the two most important SNP variants: C677T and A1298C. However, the exact role of the mentioned polymorphisms in the pathogenesis of venous thrombosis remains unclear, especially since the results of several studies conducted so far were inconsistent and did not confirm univocally any such direct relationship. In this review the authors aim to explain the reason of such a discrepancy. Moreover, the authors try to answer the question, whether both mentioned polymorphic variants of the MTHFR gene (C677T and A1298C) are in fact considerable risk factors for venous thrombosis. Based on various pro and contra published so far, the authors conclude that polymorphisms of MTHFR, although recognised as rather weak single risk factors of VT, cannot be underestimated and still require our attention.