Increased Frequency of the MTHFR A1298C Mutation in an Irish Population

Abstract

The enzyme methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of methylene tetrahydrofolate to 5-methyltetrahydrofolate, the cosubstrate required for the remethylation of homocysteine to methionine. Mutations in the MTHFR enzyme are reported as causes of hyperhomocysteinemia (1). Hyperhomocysteinemia is generally, although not universally, seen as an independent and graded risk factor for venous thrombosis and neural tube defects (2). Several polymorphisms have been reported in the MTHFR gene, but two particular mutations generate the most interest, the recently described A1298C (3) and the most-characterized C677T (4). The A1298C polymorphism in the MTHFR gene encodes for a glutamate to alanine substitution and leads to a decrease in enzyme activity. Combined heterozygosity for the C677T/A1298C polymorphisms in some studies (5) is associated with higher homocysteine concentrations and decreased plasma folate. Amplification Refractory Mutation System (ARMS) PCR determination of the MTHFR C677T mutation has been described by Hessner et al. (6). To determine the frequency of the A1298C …