Influence of interleukin 12B , interleukin 16 and interleukin 18 genes polimorphisms on delayed graft function and rejection episodes in patients after kidney transplantation

Anita Sierocka¹, Jan Pawlus¹, Zbigniew ZiÄ™tek², Karol Tejchman¹, Maciej Romanowski¹, Andrzej Pawlik³, Jerzy SieÅ„ko¹, Maciej Å»ukowski⁴, Kazimierz Ciechanowski⁵, Marek Ostrowski¹, Tadeusz Sulikowski¹

¹Department of General Surgery and Transplantation, Pomeranian Medical University, Faculty of Medicine, Szczecin, Poland, ²Chair and Department of Anatomy, Pomeranian Medical University, Faculty of Medicine, Szczecin, Poland, ³Department of Experimental and Clinical Pharmacology, Pomeranian Medical Uniwersity, Faculty of Medicine, Szczecin, Poland, ⁴Clinic of Anaesthesiology and Intensive Care, Pomeranian Medical University, Faculty of Medicine, Szczecin, Poland, ⁵Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Faculty of medicine, Szczecin, Poland

Background:Inflammatory mediators have an important role in kidney graft outcomes. The cytokine and chemokine gene polymorphisms are associated with variable production,activity,expression or ligand-receptor affinity[1]. Genetic variation in the DNA sequence of the interleukin 12B (IL-12B), interleukin 16 (IL-16) and interleukin 18 (IL-18) genes may lead to altered cytokine production and activity. These variations can lead to changes in individual's patient outcome after kidney transplantation. That is know,the polymorphisms of interleukins influence on inflammatory diseases, e.g. diabetes, asthma or periodontopathy. Nevertheless there were only few publications about their role in kidney graft outcome [2,3,4].

Aim:The aim of this study was to evaluate the correlation between IL-12B, IL-16 and IL-18 genes polimorphisms with graft function (delayed graft function-DGF) and rejection episodes-acute(AR), chronic(CR).

Materials and methods:267 (38,6% women, 61,4% men) recipients were included to the study. The polymerase chain reaction was used to determine gene polymorphisms of IL-12B(rs3212227), IL-16(4778889), IL-18(rs1946518,rs187238) in serum. Statistical sihnificance (p<0,05) was analised by logit regression (Pearson Chi², M-L Chi², Phi, Kendall's test, Gamma test, Spearman Rank R), ANOVA - Tukey's post-hoc test, Odds Ratio (OR)-Chi² with Yates correction (CI-95%).

Results:Regression analysis revealed no significance between AR/DGF/CR and IL-12B (p=,176/p=,328/p=,438), IL-16 (p=,231/p=,784/p=,287), IL-18-rs1946518 (p=,582/p=,279/p=,084), IL-18-rs187238 (p=,285/p=,279,p=,303). CR group-AAvsCC genotype (IL-18,rs1946518) OR=2,35 (p=,040).

Conclusion:There was no statistical significance between IL-12B, IL-16 and IL-18 gene polimorphisms and kidney graft outcomes after transplantation. Presence of AA genotype IL-18 (rs1946518) is connected with 2,35 higher risk of CR occurence.

Source of Funding:NCN:2013/B/P01/2011/40