The effect of recipient cytokine gene polymorphism on cardiac transplantation outcome.
We determined the association between clinical outcomes after heart transplantation and gene polymorphism in five cytokines (tumor necrosis factor-alpha, transforming growth factor (TGF)-beta, interleukin-10, interleukin-6, and interferon-gamma) reported to influence expression in vitro. Ninety-five patients were studied. Cytokine genotyping was performed by sequence specific priming polymerase chain reaction. Clinical outcomes studied in the first posttransplant year included: (1) documented viral, bacterial, or fungal infection; (2) cytomegalovirus infection; (3) acute cellular rejection (International Society for Heart and Lung Transplantation > or = grade IIIA); (4) time to first rejection episode; and (5) the development of allograft vasculopathy. Patients with the TGF-beta genotype 10 T/T 25 G/G or 10 T/C 25 G/G had a longer time to first rejection (median time to first rejection episode 321 days) than those with the TGF-beta genotype 10C/C 25 G/C or 10 C/C 25 C/C (median time to first rejection 88 days). There was a trend toward a higher frequency of the tumor necrosis factor-alpha genotype -308 G/A or A/A in patients without infection (19/59, 32%) as compared with patients with infection (5/31, 16%). In both cases, these differences failed to reach significance when adjusted for multiple comparisons. No other significant association was found with clinical outcomes and polymorphisms in the five cytokine genes studied in this population.
Gourley
Ian S
IS
University of Pennsylvania Medical Center, Philadelphia, PA, USA.
Denofrio
David
D
Rand
William
W
Desai
Shashank
S
Loh
Evan
E
Kamoun
Malek
M
D000328:Adult; D017931:DNA Primers; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007239:Infections; D007371:Interferon-gamma / Q000235:genetics; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D017931:DNA Primers; D007166:Immunosuppressive Agents; D007378:Interleukins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma