title: The impact of apoptosis and inflammation gene polymorphisms on transplanted kidney function.
abstract: BACKGROUND
  The progressive deterioration of kidney allograft function leads in most cases to transplant failure. Polymorphisms in genes encoding for inflammatory and apoptosis molecules may be one possible explanation for interindividual differences in kidney transplant outcomes. The objective of our work was to identify the possible effect of interleukin 6 (IL-6), transforming growth factor beta 1 (TGFB1), and Fas on graft function.
  
  
  METHODS
  A case-control study was carried out to assess potential associations between polymorphisms in inflammation- and apoptosis-related genes and the risk for chronic impairment of kidney graft function. The study included 376 cadaveric kidney recipients, 256 of them with stable graft function and 120 who experienced renal deterioration during the follow-up period of 2.6 ± 1.4 years. Genotyping of IL-6/G-174C, TGFB1/L10P, TGFB1/R25P, and Fas/G-670A polymorphisms was performed by PCR-RFLP and direct sequencing.
  
  
  RESULTS
  Considering the single IL-6, TGFB1, and Fas polymorphisms, we found similar allelic and genotype frequencies between the 2 groups. To test the hypothesis of mutual effects of polymorphisms, multiple logistic regression was performed incorporating data for all the possible dual genotypic associations. The association of IL-6 high producer and Fas low producer genotype resulted in a protective effect against graft dysfunction (OR=0.79; 95% C.I.=0.72-0.86).
  
  
  CONCLUSIONS
  This study did not find significant associations of apoptosis and inflammation gene polymorphisms with transplanted kidney function in Italian renal transplant recipients. However, our data seem to indicate that the carriage of IL-6 high producer/Fas low producer genotype has a protective effect against graft function loss.
authors.affiliation: Section of Nephrology and Renal Transplant, Department of Specialistic, Diagnostic and Experimental Medicine, 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: Irene
authors.initials: I
authors.lastname: Capelli
authors.forename: Olga
authors.initials: O
authors.lastname: Baraldi
authors.forename: Vania
authors.initials: V
authors.lastname: Cuna
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Battaglino
authors.forename: Giorgio
authors.initials: G
authors.lastname: Feliciangeli
authors.forename: Ada
authors.initials: A
authors.lastname: Dormi
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; D017209:Apoptosis / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000601:surgery; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult; D019014:fas Receptor / Q000235:genetics*
chemical_list: C491901:FAS protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D053773:Transforming Growth Factor beta1; D019014:fas Receptor