Cytokine production is subject to genetic regulation, in such a way that gene polymorphisms at the level of promoter or coding regions can alter their levels and thus modify the inflammatory and/or immunologic response towards any stimulus.

Objetive: To evaluate the influence of single nucleotide polymorphisms (SNPs) of IL10, TNFα, IFNγand IL18on early renal graft outcomes.

Method:Observational study that included 709 consecutive patients who received a first renal transplant at our center from January 2005 to December 201. SNP analysis was carried out by real-time PCR using Taqman® probes.Patients were stratified according to the higher production genotype. A control group that included healthy subjects was used to confirm that the genotypic data obtained conformed to the expected frequencies in accordance with the Hardy-Weinberg equilibrium.

Results: There was a significant association between SNP of TNFα -308 G/A and acute vascular rejection (AVR) in the adjusted logistic regression model.Allele A (GA/AA) carriers had nearly a threefold higher risk of developing AVR (OR=2.64; CI 95%: 1.46-4.76; p=0.001) compared to those who had GG genotype.In the analysis for risk of delayed graft function (DGF), stratified according to donor type, an association between DGF and SNP of TNFα -308 G/Ain grafts received from brain dead donors was found. A further association was observed between DGF and SNP of IL18 -137 G/C in grafts received from non-beating heart donors. Regarding renal graft recipients from brain dead donors, TNFα GA/AA genotypes had a higher risk of DGF (OR=6.15; CI 95%: 1.65-22.86; p=0.007);while in those from non-beating heart donors, G allele carriers within SNP -137 G/C of IL18 had the higher risk (OR=2.76; CI 95%: 1.03-7.40; p=0.042).

Conclusions:SNP -308G/A of TNFα can be considered as a non-invasive risk biomarker for AVR and, in grafts coming from brain dead donors, DGF.On the other hand, SNP -137G/C of IL18 was the main genetic marker for DGF in grafts from non-beating heart donors. The knowledge of these polymorphisms previous to transplantation could aid in individualizing immunosuppressant treatment to avoid the development of complications and improve outcomes.

CITATION INFORMATION: Pérez-Flores I, Santiago J, Moreno Dela Higuera A, Calvo N, Rodriguez-Cubillo B, Urcelay E, Shabaka A, Calvo M, Sanchez-Fructuoso A. Impact of Cytokine Gene Polymorphism on Clinical Outcome of Renal Transplantation. Am J Transplant. 2017;17 (suppl 3).

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