Polymorphism of folate-metabolizing enzyme correlated with coronary artery disease, says new study

Aug 17, 2018

A new study1 found a correlation between the genetic polymorphism of the enzyme methylenetetrahydrofolate reductase (MTHFR) and coronary artery disease (CAD). Researchers explain that MTHFR plays a crucial role in the metabolism of folates, converting 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate.

“5-methyltetrahydrofolate is the predominant circulatory form of folates and donates a methyl group for remethylation of homocysteine to methionine,” explained Tantray et al. in the study. “Consecutively, methionine is metabolized to yield S-adenosylmethionine [SAMe], the main methyl donor for important methylation reactions that are required for DNA repair.”

Impaired MTHFR activity can cause homocysteine accumulation in plasma, contributing to atherosclerosis through a variety of mechanisms like arterial endothelial function impairment, oxidative stress, and the promotion of inflammation and thrombosis, the researchers explain. Researchers specifically studied C677T polymorphism of MTHFR, which has previously been implicated in vascular disease.

There were 210 subjects in total in the current study, of which 100 (56 males and 44 females) presented various forms of cardiovascular disease and 110 (60 males, 50 females) were healthy controls. When DNA was extracted from blood samples, researchers found polymorphism in both the CAD group and the controls, though the presence of MTHFR C677T was more significantly associated with CAD patients along with common risk factors like smoking, hypertension, and diabetes. (Some members of the control group also had these risk factors, but without the presence of CAD.) Total cholesterol and LDL-cholesterol were also higher in the CAD group than control. Researchers concluded that MTHFR polymorphism is a major determinant of CAD, but not important as a single factor.

While it may be true that multiple factors cause CAD beyond MTHFR polymorphism, MTHFR polymorphism remains a significant factor and proper folate supplementation may combat this, according to Lorena Carboni, product support specialist for Gnosis (Desio, Italy). Gnosis supplies an ingredient called Quatrefolic, which is an active folate that does not require metabolism and bypasses the polymorphism of MTHFR, the company says.

“The role of this polymorphism in health and longevity is increasingly evident,” said Carboni in a press release. “As the manufacturers of Quatrefolic, the active folate that does not require metabolism and bypasses the polymorphism of MTHFR, we continue to devote efforts and commitment to informing about the latest scientific developments involving folate metabolism and the potential role of right supplementation.”


1. Tantray JA et al. “A study of C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene and its susceptibility in coronary artery disease.” Asian Journal of Biology, vol. 6, no. 1 (2018).