Effect of folate, vitamin B6, and vitamin B12 intake and MTHFR C677T polymorphism on homocysteine concentrations of renal transplant recipients.

Plasma hyperhomocysteinemia (HHcy) is considered a risk factor for chronic allograft dysfunction (CAD), the main cause of functional loss in transplant recipients. Genetic polymorphisms that alter enzymes involved in homocysteine (Hcy) metabolism, such as methylenetetrahydrofolate reductase (MTHFR), and vitamin deficiency can result in HHcy. The objectives of this study were to investigate the relationship between HHcy and CAD development, and to evaluate the effect of intake of folate and vitamins B6 and B12 as well as MTHFR C677T polymorphism on Hcy concentrations. Ninety-eight renal transplant recipients including 48 showing CAD and 50 with normal renal function (NRF), were included in this cross-sectional study. Peripheral blood samples were collected for plasma Hcy quantification by liquid chromatography/sequential mass spectrometry (LC-MS/MS), and for MTHFR polymorphism analysis using polymerase chain reaction-restriction fragment length polymorphism. Dietary intake was evaluated using a nutritional questionnaire. HHcy (P=.002) and higher mean concentrations of Hcy (P=.029) were associated with CAD. An association was observed between HHcy and 677T variant allele in the CAD group (P=.0005). There was no correlation between Hcy concentration and folate, vitamin B6 or vitamin B12 intake in the CAD group. However, a negative correlation was observed between Hcy concentration and folate intake (P=.043), and also between Hcy concentration and vitamin B6 intake (P=.030) in the NRF group. According to our study, HHcy is associated with CAD development. In patients with CAD, MTHFR polymorphism seems to have a greater effect on the Hcy concentration than the vitamin intake. Increased folate and vitamin B6 intakes seem to reduce Hcy concentrations among transplant recipients with NRF, and could contribute to reducing the risk of CAD development.

Hyperhomocysteinemia and MTHFR C677T and A1298C polymorphisms are associated with chronic allograft nephropathy in renal transplant recipients.

Hyperhomocysteine has been reported to be an important risk factor for the development of atherosclerosis. Identification of risk factors, such as hyperhomocysteinemia, is crucial for a better understanding of the events that lead to degenerative processes in the vascular system and for a correct understanding of the potential role of methylene-tetrahydrofolate reductase enzymes (MTHFR) to help in the treatment of vascular disease observed in chronic allograft nephropathy (CAN). In this study we analyzed the plasma homocysteine concentrations and MTHFR C677T and A1298C polymorphism frequencies among 110 renal transplant recipients (53 with CAN and 57 with normal renal function). All recipients had undergone renal transplantation at least 12 months prior to this investigation to establish a possible correlation with the posttransplant outcome. Plasma homocysteine concentrations were measured by liquid chromatography-tandem mass spectrometry and MTHFR polymorphisms were investigated by the PCR-RFLP technique. The results demonstrated that in renal transplant recipients, hyperhomocysteinemia in addition to the presence of the allelic variants for both MTHFR polymorphisms (677T/1298C) might play a role as an additional risk factor for CAN. We understand that analysis of these polymorphisms might have a role in the CAN process. Therefore, studies to evaluate their presence in renal transplant patients may be extremely useful to individualize immunosuppressive protocols to inhibit or retard the progression of CAN.