Methylenetetrahydrofolate-reductase gene C677T variant and kidney-transplant survival

Background. Hyperhomocysteinaemia, a risk factor for atherosclerosis, is common in haemodialysis and renal-transplant patients. As atherosclerotic lesions in hyperhomocysteinaemia resemble those of chronic allograft injury, we examined the hypothesis that the C677T variant of the methylenetetrahydrofolate reductase (MTHFR) gene, which is linked to elevated plasma homocysteine levels in patients with renal failure, determines renal allograft survival. Methods. DNA was prospectively collected from 336 patients undergoing renal transplantation in our clinic between 1988 and 1994 and their corresponding donors. Patient and allograft survival was analysed by blinded review of all case records over a follow-up period of 36 months. Additionally, we recruited 83 patients surviving with a functional kidney allograft for at least 10 years (mean, 156, range 120-240 months). MTHFR-C677T genotype was determined by a PCR-RFLP technique. The influence of genotype on transplant survival was analysed by Kaplan-Meyer life-table analysis and two-tailed global log-rank testing. Results. Frequency of the MTHFR-C677T allele in the cohort group was identical in recipients (0.35) and donors (0.34), and comparable to that in the longterm allograft survivors (0.37). Furthermore, life-table analysis revealed a similar allograft survival over 36 months between the genotype groups (CC 74%, CT 69%, TT 75%). Other risk factors including donor and recipient age,hypertension, body-mass index, and number of rejection therapies were evenly distributed between the different genotype groups. Conclusions. These findings do not support the hypothesis that the C677T variant of the MTHFR gene is an important determinant of renal-transplant survival.