MTHFR Polymorphisms and Disease

Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in both folate and homocysteine metabolism. It first achieved medical recognition in 1972 with the report of severe deficiency of MTHFR in a patient with homocystinuria, an inborn error of metabolism characterized by marked elevation of homocyst(e)ine in plasma and urine. Although the majority of cases of homocystinuria are due to a deficiency of the first enzyme in the transsulfuration pathway for homocysteine metabolism, cystathionine-ß-synthase (CBS), disruption of homocysteine remethylation to methionine can also result in homocystinuria. With the identification of additional patients with severe MTHFR deficiency, the heterogeneity of this disorder became manifest.

This book covers many of the complex traits that have been reported to be influenced by the well-characterized 677C→T variant; there is less information on the 1298A→C variant, but it is discussed where appropriate. It is quite surprising, and unique, that a single variant should influence such a wide variety of clinical conditions.