The common mutations C677T and A1298C in the human methylenetetrahydrofolate reductase gene are associated with hyperhomocysteinemia and cardiovascular disease in hemodialysis patients.

BACKGROUND: Plasma total homocysteine (tHcy) level might be an important risk factor for the development of cardiovascular disease (CVD) in dialysis patients. While both renal failure and mutations of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene may result in hyperhomocysteinemia and CVD, the distinct roles of the thermolabile MTHFR mutation at nucleotide C677T and the more recently described mutation at nucleotide A1298C have not been evaluated concurrently in patients on hemodialysis.
METHODS: A cross-sectional study was performed in 120 maintenance HD patients to determine the prevalence of MTHFR C677T and A1298C mutations and their relative association to hyperhomocysteinemia and CVD.
RESULTS: Both mutations, the C677T and the A1298C, were highly prevalent in HD patients with allele frequencies of 0.41 and 0.27, respectively. The prevalence of CVD in HD patients was 55% and its significant risk factors included, in descending order, hyperhomocysteinemia, MTHFR C677T mutation, low serum folate levels, diabetes mellitus, hypertension, and double heterozygote state for both MTHFR mutations (677CT/1298AC). MTHFR A1298C mutation alone and gender were not associated with either hyperhomocysteinemia or increased CVD risk, but the HD patients with homozygotes 1298CC and wild alleles 677CC (677CC/1298CC) have significant increase of tHcy (37.7 +/- 12) and high prevalence of CVD.
CONCLUSIONS: Hyperhomocysteinemia, serum folate levels and both C677T and A1298C MTHFR mutations are associated with CVD in HD patients. Copyright 2002 S. Karger AG, Basel