Influence of cytokine genes polymorphisms on long-term outcome in renal transplantation

Abstract: Background: Recently, polymorphisms of cytokine genes have been associated with modified gene expression and increased cytokine production. We evaluated the influence of interleukin-10 (IL-10) gene G-1082A, tumour necrosis factor alpha (TNFα) gene G-308A and IL-6 gene G-174C polymorphisms on the rejection rate, renal function and long-term outcome in renal transplantation.

Patients and methods: We studied n = 224 consecutive patients, who underwent renal transplantation at our centre from 1998 to 2001 (cadaveric: n = 175, living related: n = 49) followed up for 4.9 ± 2.0 yr and n = 100 healthy volunteers. IL-10 gene G-1082A, TNFα gene G-308A and IL-6 gene G-174C polymorphisms were determined by polymerase chain reaction (PCR) amplification.

Results: The genotype distribution of the investigated polymorphisms was similar in patients and controls (ns). The age of donor and the recipient, the number of HLA mismatches and cold and warm ischemic time did not differ among patients with different genotypes (ns). No association between cytokine polymorphisms and the incidence of acute rejection episodes was detected (ns). The cytokine genotypes did not correlate with serum creatinine or creatinine clearance at any time during follow up (ns). Furthermore, there was no significant difference in the genotype frequencies among patients experiencing graft failure (ns). Patients with different cytokine gene polymorphisms showed similar outcomes in the Kaplan–Meier analysis of graft survival (ns). Finally, cytokine polymorphisms had no influence on the acute rejection rate or graft outcome also in the subgroup of HLA-DR mismatched grafts (ns).

Conclusion: Our results suggest that IL-10 gene G-1082A, TNFα gene G-308A and IL-6 gene G-174C polymorphisms are no major risk factors in renal transplantation.