Impact of VKORC1 haplotypes on long-term graft function in kidney transplantation.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Quteineh
Lina
L
Pharmacology Department, Pierre and Marie Curie University, Saint Antoine University Hospital, Paris, France. lina.quteineh@yahoo.com
Verstuyft
Celine
C
Durrbach
Antoine
A
Letierce
Alexia
A
Ferlicot
Sophie
S
Charpentier
Bernard
B
Becquemont
Laurent
L
D000328:Adult; D016001:Confidence Intervals; D005260:Female; D005838:Genotype; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000453:epidemiology; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology / Q000401:mortality / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011507:Proteinuria; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D064417:Vitamin K Epoxide Reductases
D006899:Mixed Function Oxygenases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases