Impact of VKORC1 Haplotypes on Long-Term Graft Function in Kidney Transplantation

Abstract

Chronic allograft injury is the major cause of renal allograft loss after the first year of transplantation. Vitamin K epoxide reductase complex subunit 1 (VKORC1) haplotype combinations were found to be associated with the risk of developing vascular diseases. We aimed to study the effect of VKORC1 haplotypes on long-term graft function in a cohort of kidney transplant recipients. A total of 288 renal allograft recipients participated in the study. Long-term renal graft function was measured by the estimation of the glomerular filtration rate. VKORC1 C+1173T single nucleotide polymorphism (rs9934438) was used as a tagging single nucleotide polymorphism for VKORC1*2 haplotype. Patients homozygous for VKORC1*2 haplotype showed less deterioration of renal graft function compared with the other patients (hazard ratio: 0.34, 95% confidence interval: 0.26-0.87, P=0.02). The same results were obtained in a multivariate analysis, where VKORC1 haplotypes showed to be an independent predictor of long-term graft function when adjusted to other variables contributing to long-term renal graft outcome. Our results suggest that VKORC1 haplotypes may play a role in the long-term renal allograft function. These findings need to be replicated in prospective clinical studies.