Association Interleukin-4 and Interleukin-4 Receptor Gene Polymorphism and Acute Rejection and Graft Dysfunction After Kidney Transplantation.

ABSTRACT

BACKGROUND: Cytokine 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. METHODS: We 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. RESULTS: The 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. CONCLUSIONS: One 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.