Immune response gene polymorphisms in renal transplant recipients.
BACKGROUND
T-cell activation and regulation are under genetic control and vary between individuals. However, the influence of functional immune response gene polymorphisms on transplant outcomes remains controversial.


METHODS
A case-control design compared 100 white renal transplant recipients with or without acute graft rejection during the first year posttransplant and 50 normal controls. The polymorphic frequencies of the T-cell signaling genes CD45, CD40L and CTLA-4, and the cytokine genes TNF-alpha, IFN-gamma, IL-10 and TGF-beta1 were studied. The primary analysis examined rejection risk, and subsidiary analyses graft failure and patient death.


RESULTS
Multivariate analysis showed no significant association between acute rejection and single nucleotide polymorphisms in CTLA-4, TGF-beta1, IL-10 or TNF-alpha genes or dinucleotide repeat polymorphisms in IFN-gamma and CD40L genes. Allele CD40L-147 was associated with reduced graft failure (P=0.004), and TGFb-25pro with increased graft failure (P=0.0007), although the latter showed a bidirectional dose effect. There was no significant association between patient death and any polymorphisms in the genes examined. The variant (G) allele of the CD45 gene was not detected in the study population. Minor differences in carriage rates observed by univariate analysis did not predict graft or patient outcome in multivariate analysis.


CONCLUSIONS
The primary analysis demonstrated no significant association between the immune response gene polymorphisms examined and acute renal graft rejection in Caucasian patients receiving triple immunosuppression. Subsidiary analyses suggesting an influence of CD40L and TGFbeta1 genes on graft survival require independent confirmation.
Dmitrienko
Svetlana
S
Immunology Laboratory, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Hoar
David I
DI
Balshaw
Robert
R
Keown
Paul A
PA
D019943:Amino Acid Substitution; D015703:Antigens, CD / Q000235:genetics*; D000943:Antigens, Differentiation / Q000235:genetics; D060908:CTLA-4 Antigen; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D013601:T-Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma