Association of donor TNFRSF6 (FAS) gene polymorphism with acute rejection in renal transplant patients: a case-control study.
BACKGROUND
Genetic factors other than HLA have been reported to be associated with the outcome of organ transplantations. Because binding of FasL to its receptor Fas could play an important role in tubulitis and in the death of graft tubular epithelial cells during kidney allograft rejection, a gene polymorphism recently identified in position -671 in the promoter of the TNFRSF6 gene coding for Fas was investigated in donors.


METHODS
A case-control study was performed within a cohort of non-hyperimmunized adult patients who had received cadaveric kidney transplants based on the occurrence or absence of acute cellular rejection in the first 6 months after renal transplantation. Each recipient from the acute rejection group (n = 35) was matched for age (+/- 5 years) and number of HLA-DR mismatches with two recipients within the non-acute rejection group (n = 70).


RESULTS
The TNFRSF6-GG genotype was more frequent in donors in the group without rejection episodes. In contrast, patients who received a kidney from a TNFRSF6-A carrier were more likely to experience acute rejection episodes (relative risk nearly 2.1).


CONCLUSIONS
This study suggests that donor TNFRSF6 polymorphism directly or indirectly influences acute kidney rejection episodes.
Cappellesso
Sandrine
S
UPRES-EA 3249 Cellules Hématopoïétiques, Hémostase et Greffe, Université de Tours, Faculté de Médecine, and Laboratoire d'Immunologie and Service de Néphrologie et Immunologie Clinique, CHRU de Tours, Tours cedex, France.
Valentin
Jean-François
JF
Giraudeau
Bruno
B
Boulanger
Marie-Denise
MD
Al-Najjar
Azmi
A
Büchler
Mathias
M
Halimi
Jean-Michel
JM
Nivet
Hubert
H
Bardos
Pierre
P
Lebranchu
Yvon
Y
Watier
Hervé
H
D000328:Adult; D000704:Analysis of Variance; D001483:Base Sequence; D016022:Case-Control Studies; D005260:Female; D006084:Graft Rejection / Q000235:genetics*; D006085:Graft Survival; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000601:surgery; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000379:methods; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011336:Probability; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D011506:Proteins / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D014019:Tissue Donors; D019014:fas Receptor
C491901:FAS protein, human; D006684:HLA-DR Antigens; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor