A common mutation A1298C in human methylenetetrahydrofolate reductase gene: Association with plasma total homocysteine and folate concentrations

Methyleneletrahydrofolate reductase (MTHFR) is one of the main regulatory e nzymes of homocysteine metabolism. Previous studies revealed that a common mutation in MTHFR gene C677T is related to hyperhomocysteinemia and occlusi ve vascular pathology. In the current study, we determined the prevalence o f a newly described mutation in the human MTHFR gene A1298C, and the alread y known C677T mutation, and related them to plasma total homocysteine and f olate concentrations. We studied 377 Jewish subjects, including 190 men and 186 women aged 56.8 +/- 13 y (range 32-95 y). The frequency of the homozyg otes for the A1298C and the C677T MTHFR mutations was common in the Jewish Israeli population (0.34 and 0.37, respectively). Subjects homozygous (TT) for the C677T mutation had significantly greater plasma total homocysteine concentrations (P < 0.01) than subjects without the mutation (CC). Homozygo tes (CC) for the A1298C mutation did not have elevated plasma total homocys teine concentrations. Our study indicated that subjects with the 677CC/ 129 8CC genotype had significantly lower concentrations (P < 0.05) than those w ith a 677CC/1298AA genotype. Neither mutation (the A1298C and the C677T) wa s associated with established cardiovascular risk factors such as hypertens ion, elevated total cholesterol or body mass index.