5, 10-MTHFR (C677T) Gene Polymorphism and Total Homocysteine Levels in Renal Transplant Recipients

Abstract

701 Hyperhomocysteinemia is an important cardiovascular risk factor and may be aggravated by a polymorphism (C677T) in the gene coding for 5,10-methylenetetrahydrofolate reductase (MTHFR). The effect of this gene defect on total homocysteine (tHcy) and folate plasma levels in renal transplant patients is unknown. We investigated the impact of the kidney recipient and kidney donor MTHFR gene polymorphism on tHcy and folate plasma levels in 111 kidney graft recipients. Vitamin B12 levels, age, gender, glomerular filtration rate and body mass index were recorded in all patients. The (C677T) substitution in the MTHFR gene significantly influenced tHcy plasma concentrations in renal transplant recipients (p = 0.05). Furthermore, there was a significant influence of the glomerular filtration rate(64.9±15.8 ml/min, p = 0.001) and folate levels (14.6±6.9 nmol/l, p = 0.005) on tHcy concentrations, whereas the donor MTHFR gene polymorphism, vitamin B12 levels, age, gender, body mass index and time since transplantation showed no effect by analysis of covariance. The geometric mean tHcy level in patients homozygous for the mutant MTHFR allele(n=14) was 16.5 μmol/l compared to 12.9 μmol/l and 13.5 μmol/l in patients heterozygous for the MTHFR polymorphism (n=35) and those with normal alleles (n=62). The geometric mean of tHcy plasma levels in patients with excellent kidney graft function (glomerular filtration rate > sample median) who were homozygous for the mutant MTHFR allele was 17.6 μmol/l versus 11.2 μmol/l in heterozygotes and 12.9 μmol/l in patients homozygous for the normal allele. In individuals with moderately impaired graft function (glomerular filtration rate < sample median) the geometric mean tHcy concentration was 15.5 μmol/l versus 15.1 and 14.2 μmol/l in heterozygotes and patients without polymorphism. In patients and kidney donors homozygosity for the MTHFR gene polymorphism revealed a tendency towards lower folate levels of kidney graft recipients. The (C677T) polymorphism in the MTHFR gene significantly increases tHcy concentrations in kidney graft recipients. The homozygous mutant MTHFR alleles of the donor kidney were associated with a trend to lower folate levels. These findings may have important implications for risk evaluation and vitamin intervention in these patients who carry an increased risk for development of cardiovascular disease.