14th Congress of the Asian Society of TransplantationKidneyAssociation Interleukin-4 and Interleukin-4 Receptor Gene Polymorphism and Acute Rejection and Graft Dysfunction After Kidney Transplantation

•It have previously been found that allograft outcomes determined, in part, by alloimmune responses are mainly mediated by T-cell responses activated and driven by cytokines. There has been no study of the genetic associations of the interleukin-4 (IL-4) gene and the IL-4 receptor (IL-4R) gene in Korean renal allograft recipients. This study was the first evaluation of the association between IL-4 and IL-4R single nucleotide polymorphism and acute rejection (AR) or graft failure (GF) in renal transplant patients.•We report 3 major findings: (1) rs1801275 of the IL-4R gene exhibited a significant association with AR in a co-dominant model, a dominant model, and a log-addictive model; (2) rs2107356 of the IL-4R single nucleotide polymorphism was statistically associated with GF in the dominant model; and (3) no significant differences in genotypes of the IL-4 gene were observed between AR/GF and non-AR/non-GF subjects.

BackgroundCytokine genotypes have previously been studied in patients undergoing solid organ transplantation; certain polymorphisms have been implicated in the development of acute rejection (AR) and graft dysfunction (GD). Allograft outcomes determined, in part, by alloimmune responses is mainly mediated by T-cell responses, activated and driven by cytokines. Interleukin-4 (IL-4) is one such cytokine, which exerts its biological effects through binding to the IL-4 receptor (IL-4R) complex on target cells. In the present study, we investigated whether polymorphisms of the IL-4 and/or IL-4R gene were associated with susceptibility to acute AR and GD after kidney transplantation.MethodsWe analyzed 2 single nucleotide polymorphism (SNPs) of IL-4 (rs2243250 and rs2070874) and 3 SNPs of IL-4R (rs1801275, rs2107356, and rs1805010) in 344 kidney transplant recipients. These patients included 62 of whom had developed AR and 215 of whom had GD in 1 year after kidney transplantation.ResultsThe AR group included 62 patients (45 men and 17 women). There was a statistically significant difference in the male-to-female ratio and the use of tacrolimus in the AR group. The GD group included 215 patients. Patients who developed GD were more likely to be older and have an underlying cause of end-stage renal disease that was unknown compared with patients who did not have GD, the cause of which was typically known. Among the SNPs examined, 1 of the SNPs in the IL-4R gene (ie, rs1801275) showed a statistical association with AR (co-dominant model, P = .061; dominant model, P = .019; and log-addictive model, P = .029). In addition, 1 of the IL-4R SNPs (ie, rs2107356) was statistically associated with GD (dominant model, P = .034). No significant difference in the IL-4 genotype was observed between the AR/GD and non-AR/non-GD subjects.ConclusionsOne IL-4R gene polymorphism (rs1801275) was associated with AR. In addition, a separate IL-4R SNP (rs2107356) was statistically associated with GD after kidney transplantation.