title: 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.
authors.affiliation: Department of Nephrology, Seoul Red Cross Hospital, Seoul, Republic of Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Nephrology, School of Medicine, Inje University, Busan, Republic of Korea.
authors.forename: T H
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Nephrology, School of Medicine, Inje University, Busan, Republic of Korea.
authors.forename: S W
authors.initials: SW
authors.lastname: Kang
authors.affiliation: Department of Nephrology, School of Medicine, Inje University, Busan, Republic of Korea.
authors.forename: Y H
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Kohwang Medical Research Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: S K
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Kohwang Medical Research Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Chung
authors.affiliation: Department of Nephrology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Y G
authors.initials: YG
authors.lastname: Kim
authors.affiliation: Department of Nephrology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: J Y
authors.initials: JY
authors.lastname: Moon
authors.affiliation: Department of Nephrology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Nephrology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: C G
authors.initials: CG
authors.lastname: Ihm
authors.affiliation: Department of Nephrology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: T W
authors.initials: TW
authors.lastname: Lee
authors.affiliation: Department of Nephrology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea. Electronic address: khjeong@khu.ac.kr.
authors.forename: K H
authors.initials: KH
authors.lastname: Jeong
mesh_terms: D000328:Adult; D044466:Asian People; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics*; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D016030:Kidney Transplantation; D008297:Male; D020641:Polymorphism, Single Nucleotide; D055031:Primary Graft Dysfunction / Q000235:genetics*; D019948:Receptors, Interleukin-4 / Q000235:genetics*; D056910:Republic of Korea
chemical_list: D019948:Receptors, Interleukin-4; D015847:Interleukin-4