title: Donor interleukin-4 promoter gene polymorphism influences allograft rejection after heart transplantation.
abstract: BACKGROUND
  The cytokine interleukin-4 (IL-4) is secreted mainly by activated T lymphocytes and characterizes the T-helper 2 (Th2) sub-type. In transplantation Th2 cells are believed to induce graft tolerance. Previous studies revealed that patients with a relatively high frequency of IL-4 producing helper T lymphocytes (HTL) before heart transplantation (HTX) had no or less rejection episodes compared with patients with a low frequency of IL-4 producing HTL. Three single nucleotide polymorphisms (SNPs) have been identified in the promoter region of the IL-4 gene, which influence promoter strength. We investigated whether there was a correlation between SNP genotypes in the IL-4 promoter and heart failure, and rejection after HTX.
  
  
  METHODS
  Seventy HTX patients, 61 donors, and 36 controls were genotyped for the 3 SNPs by sequencing.
  
  
  RESULTS
  Of the SNPs at -285 and -81, only the C and A alleles, respectively, were found in this study. Both alleles were found for the -590 SNP. No relation between patient genotype of the SNP at -590 and heart failure and rejection was found. However, incidence of rejection was significantly lower in patients that received a donor heart with the T-positive genotype compared with patients that received a heart from a T-negative donor. Patients who had the T-negative genotype and received a heart from a T-positive donor, suffered significantly less from rejection than T-negative patients that received a T-negative donor heart. This was not significant in the T-positive patient group.
  
  
  CONCLUSIONS
  This indicates that IL-4 production within the donor heart and by cells from the donor is important for reducing incidence of episodes of rejection.
authors.affiliation: Department of Pathology University Medical Center Utrecht, Utrecht, The Netherlands. f.bijlsma@lab.azu.nl
authors.forename: Femke J
authors.initials: FJ
authors.lastname: Bijlsma
authors.forename: Joyce
authors.initials: J
authors.lastname: vanKuik
authors.forename: Marcel G J
authors.initials: MG
authors.lastname: Tilanus
authors.forename: Nicolaas
authors.initials: N
authors.lastname: deJonge
authors.forename: Erik H
authors.initials: EH
authors.lastname: Rozemuller
authors.forename: Jan G
authors.initials: JG
authors.lastname: van den Tweel
authors.forename: Frits H J
authors.initials: FH
authors.lastname: Gmelig-Meyling
authors.forename: Roel A
authors.initials: RA
authors.lastname: deWeger
mesh_terms: D000483:Alleles; D002311:Cardiomyopathy, Dilated / Q000601:surgery; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics* / Q000517:prevention & control; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D008297:Male; D017202:Myocardial Ischemia / Q000601:surgery; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D015847:Interleukin-4