Polymorphism and Cognition: The Example of Folate and MTHFR C677T

There is an increasing awareness that there is a large range of variables that will dictate the extent to which humankind develops neuropathologies. Some of this variability is due to environmental factors such as diet, while others are genetic. Polymorphisms are one area that is gaining more widespread investigations driven in part by emerging technologies and advances in high throughput analytical platforms. Here we illustrate the importance of this genetic variability in terms of a dietary component and thus describe polymorphisms for folate metabolism in relation to cognition. Folate, a kind of water-soluble vitamin, remains a dietary essential. General physiological function of folate includes forming normal embryogenesis, producing new erythrocytes, participating in DNA methylation, immune and cognitive function. Folate is required to maintain homocysteine at low levels in the central nervous system. Hyperhomocysteinemia has been associated with increased risks to psychic and neurodegenerative disorders including depression, schizophrenia, Alzheimer’s disease, and Parkinson’s disease. Proposed mechanisms for folate deficiency to affect cognition include direct neurotoxic effects of elevated homocysteine, as well as homocysteine-independent mechanisms such as decreases in the synthesis of S -adenosylmethionine. Polymorphism of 5,10-methylene-tetrahydrofolate reductase (MTHFR) C677T, a common missense polymorphism in the MTHFR gene, is associated with higher levels of plasma total homocysteine. While an elevated homocysteine level contributes to cognitive decline, MTHFR C677T polymorphism may give insight into the relation between folate and cognitive performance.