Association of methylenetetrahydrofolate reductase T677 allele with early development of chronic allograft nephropathy

Abstract

Objectives: The aim of this study was to evaluate the role of genetic polymorphisms on the development of chronic allograft nephropathy (CAN). Design and methods: Using the polymerase chain reaction (PCR), polymorphisms of methylenetetrahydrofolate reductase (MTHFR C677T), interleukin-6 (IL-6 G-174C) and CD14 (C-260T) were evaluated in 92 kidney transplant recipients with stable renal graft function and no signs of acute rejection in a protocol that included graft biopsy at 12 months after kidney transplantation. A normal population sample ( n = 365) was also included. Multivariate analysis was used to evaluate the effect of different variables on the CAN appearance. Results: There were no differences in alleles and genotypes distribution between transplant group and normal population sample. The CAN+ group ( n = 69) significantly differed from CAN− ( n = 23) in both MTHFR ( P < 0.05) and IL-6 ( P < 0.01) genotype distribution. Using logistic regression multivariate analysis, MTHFR T677 allele (OR: 3.91, CI: 1.11–13.8; P < 0.05), patient age (OR: 0.94, CI: 0.88–0.98; P < 0.01) and proteinuria (OR: 3.63, CI: 1.25–10.6; P < 0.05) were associated with CAN. Although the IL-6 G-174 allele was shown to be associated with CAN development in univariate analysis ( P < 0.01), the multivariate analysis did not show an association. There was no relation between CD14 gene polymorphism and CAN. Conclusion: The MTHFR T677 allele is associated with the presence of CAN in kidney graft biopsies 12 months after transplantation.