Impact of donor-dependent genetic factors on long-term renal graft function.
Our aim was to study the association of donor genetic features with long-term graft function as well as the impact of donor age, gender compatibility, cold ischemia time (CIT), and delayed graft function (DGF). We observed the outcomes of 125 kidney recipients for a minimum of 12 months (mean, 30.9 +/- 13.0 months). Grafts were obtained from 89 donors who underwent profiling for AHSG 1/2, MMP9 -1562C/T, IL6 -174G/C, IL1beta 3954C/T, MTHFR 677C/T, MTHFR 1298A/C, NOS3 -786C/T, and PAI1 4G/5G single-nucleotide polymorphisms (SNPs) using sequence-specific probe (SSP) polymerase chain reaction (PCR) and MPO -463G/A and CRP -390C/T/A with restriction fragment length polymorphism (RFLP) analysis. NOS3 IVa/b VNTR polymorphism was genotyped by gel electrophoresis of the respective PCR-generated DNA fragment. The presence of the aa eNOS genotype was connected with worse graft function. The aa genotype was also linked to acute rejection episodes. The lowest values of glomerular filtration rate (GFR) were displayed by recipients of grafts from donors with homozygotic PAI1 gene 5G polymorphism, linking paradoxically with lower PAI-1 synthesis suggesting that the intensity of proteolysis led to increased alloantigen specificity stimulating alloresponses. Graft function depended significantly on donor age with an influence of gender matching. GFR showed a significant dependence on DGF. Genetic features of the donor influenced long-term graft function. Variant eNOS gene polymorphism, which produced decreased eNOS activity, was linked to worse remote graft function. A similar negative impact was observed in the case of donor PAI1 polymorphism, with the functional consequence of lower gene product synthesis.
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, ul. Traugutta 57/59, 50-417 Wroclaw, Poland. magda@softstar.pl
M
M
Krajewska
K
K
Kościelska-Kasprzak
W
W
Weyde
D
D
Drulis-Fajdasz
K
K
Madziarska
O
O
Mazanowska
M
M
Kusztal
M
M
Klinger
D000328:Adult; D051799:Delayed Graft Function / Q000235:genetics*; D020869:Gene Expression Profiling; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000235:genetics*; D006085:Graft Survival / Q000235:genetics* / Q000502:physiology; D006680:HLA Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D016030:Kidney Transplantation / Q000502:physiology*; D008214:Lymphocytes / Q000502:physiology; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D014019:Tissue Donors / Q000706:statistics & numerical data*; D016896:Treatment Outcome
D006680:HLA Antigens; D006684:HLA-DR Antigens; D017395:Plasminogen Activator Inhibitor 1; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III