title: Cardiovascular disease in kidney transplant recipients: the prognostic value of inflammatory cytokine genotypes.
abstract: BACKGROUND
  Cardiovascular disease (CVD) represents the main cause of morbidity and mortality after renal transplantation. In view of the modern paradigm of atherosclerosis as an inflammatory disease, this study investigated the impact of inflammatory cytokine polymorphisms on posttransplant CVD.
  
  
  METHODS
  The association between cytokine polymorphisms and CVD was assessed in a case-control study to identify the differences in genotype distributions between kidney allografts with or without posttransplant CVD. To validate our results in two independent groups, we divided a cohort of 798 renal transplant recipients according to geographic area: an evaluation cohort of 478 patients from Emilia-Romagna and a validation cohort of 320 patients from the rest of Italy. Tumor necrosis factor (TNF)-alpha, transforming growth factor-beta1, interleukin (IL)-10, IL-6, interferon-gamma, and IL-8 polymorphisms were analyzed, and thereafter, the cytokine production genotype was assigned.
  
  
  RESULTS
  In the evaluation cohort, the patients in the CVD and no-CVD groups differed significantly in TNF-alpha and IL-10 genotype frequencies. Using multivariate analyses to test the association with CVD, the TNF-alpha high-producer genotype was associated with a significantly increased cardiovascular risk (odds ratio [OR]=4.41, 95% confidence interval (CI)=2.53-7.67). Conversely, the IL-10 high-producer genotype resulted protective against CVD (OR=0.07, 95% CI=0.02-0.29). These findings were confirmed in the validation cohort where the carriers of the TNF-alpha high-producer genotype proved to be at 2.45-fold increased cardiovascular risk (OR=2.45, 95% CI=1.29-4.63), whereas the IL-10 high-producer genotype was associated with a 0.08-fold reduced risk (OR=0.08, 95% CI=0.02-0.36).
  
  
  CONCLUSIONS
  This work suggests a prognostic value of TNF-alpha and IL-10 genotypes, which might represent cardiovascular risk markers in renal transplant.
authors.affiliation: Department of Internal Medicine, Aging and Renal Diseases, University of Bologna, Bologna, Italy. gaetano.lamanna@unibo.it
authors.forename: Gaetano
authors.initials: G
authors.lastname: La Manna
authors.forename: Maria L
authors.initials: ML
authors.lastname: Cappuccilli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cianciolo
authors.forename: Diletta
authors.initials: D
authors.lastname: Conte
authors.forename: Giorgia
authors.initials: G
authors.lastname: Comai
authors.forename: Elisa
authors.initials: E
authors.lastname: Carretta
authors.forename: Maria P
authors.initials: MP
authors.lastname: Scolari
authors.forename: Sergio
authors.initials: S
authors.lastname: Stefoni
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D016753:Interleukin-10 / Q000235:genetics; D007558:Italy; D016030:Kidney Transplantation / Q000276:immunology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D016207:Cytokines; C508609:IL10 protein, human; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10