The methylenetetrahydrofolate reductase C677T polymorphism and the risk of congenital heart diseases: a literature review

Congenital Heart Diseases (CHDs) are the most common and serious developmental anomaly and the leading non-infectious cause of mortality in the first year of life. Despite the advances in diagnosis and treatment, understanding of the developmental causes and aetiologies of CHDs has been limited. The hyperhomocysteinemia is one of the proved risk factors related to the occurrence of CHDs. The connection between cardiac defects, folate and hyperhomocysteinemia could be explained by a mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. Indeed, the C677T MTHFR mutation produces a thermolabile variant of MTHFR with reduced enzymatic action resulting in higher plasma levels of homocysteine, especially in individuals with low - folate levels. Studies regarding MTHFR C677T polymorphism in relation to CHDs have yielded conflicting conclusions. Our aim is to perform a literature review about the suspected interrelation between MTHFR C677T mutation and the risk of congenital heart diseases. Furthermore, considering that exist populations with a higher prevalence of these type of mutation, we have started a multicentre case-control study in order to further elucidate this topic.