title: Cytokine gene polymorphisms and risks of acute rejection and delayed graft function after kidney transplantation.
abstract: BACKGROUND
  Pretransplantation identification of patients at an increased risk for adverse events would allow more individualized treatment strategies possibly improving long-term outcome. We studied cytokine gene polymorphisms of kidney allograft recipients and their donors to identify factors predisposing for acute rejection (AR) and delayed graft function (DGF).
  
  
  METHODS
  A total of 291 adult cadaver kidney recipients transplanted at a single transplantation centre between 1999 and 2002 were investigated. Recipients and donors were typed for TNF-alpha(-308G/A), TGF-beta1(codon 10T/C, codon 25C/G), IL-10(-1082G/A, -819C/T, -592C/A), IL-6(-174C/G), and IFN-gamma(+874T/A) polymorphisms using a SSP-PCR kit. An AR episode was defined based on clinical and histological findings (Banff criteria). RESULTS.: The incidence of AR was 17%. In univariate statistical analyses recipients with TNF-alpha -308AA-genotype were found to be at a significantly increased risk for rejection (odds ratio [OR] 5.0, 95% CI 3.0-8.3, P = 0.003). The association was independent from the patient-donor HLA-mismatch status. In addition, patients with IL-10 ACCACC, ATAATA, GCCATA (-1082A/G, -819C/T, -592C/A, respectively) haplotypes were predisposed to rejection (OR 1.9, 95% CI 1.1-3.1, P = 0.016). Further, the combination of recipient TGF-beta1 25GG-genotype and donor IL-10 -819T-allele was associated with rejection (OR 1.8, 95% CI 1.1-3.0, P = 0.027). These variables remained significant risk factors also in a multivariate logistic regression analysis. The incidence of DGF was 22%. The risk was increased by a donor TNF-alpha -308GA-genotype (OR 1.6, 95% CI 1.1-2.6, P = 0.040).
  
  
  CONCLUSIONS
  Our results confirm that cytokine gene polymorphisms influence the outcome of kidney transplantation. Our data especially identify the TNF-alpha -308AA-genotype as a factor predisposing for AR episodes.
authors.affiliation: Stem Cell and Transplantation Services, Finnish Red Cross Blood Service, Kivihaantie 7, SF-00310 Helsinki, Finland. jarmon.laine@veripalvelu.fi
authors.forename: Noora S
authors.initials: NS
authors.lastname: Alakulppi
authors.forename: Lauri E
authors.initials: LE
authors.lastname: Kyllönen
authors.forename: Virva T
authors.initials: VT
authors.lastname: Jäntti
authors.forename: Irma H
authors.initials: IH
authors.lastname: Matinlauri
authors.forename: Jukka
authors.initials: J
authors.lastname: Partanen
authors.forename: Kaija T
authors.initials: KT
authors.lastname: Salmela
authors.forename: Jarmo T
authors.initials: JT
authors.lastname: Laine
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology*; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors
chemical_list: D016207:Cytokines