title: hTERT, BICD1 and chromosome 18 polymorphisms associated with telomere length affect kidney allograft function after transplantation.
abstract: OBJECTIVE
  It has been confirmed that telomere length (TL) correlates with chronological donor age and that telomere shortening is accelerated in allografts. The aim of this study was to analyse the associations between graft rs2735940 hTERT and rs2630578 BICD1 gene polymorphisms and rs7235755/rs2162440 chromosome 18 polymorphisms, relative TL and kidney function after transplantation.
  
  
  METHODS
  The study enrolled 119 Polish Caucasian kidney allograft recipients (64M/55F, mean age 47.3±14.0 years). The relative TL was assessed in biopsy specimens. To identify genotypes of the studied polymorphisms, real-time PCR was performed.
  
  
  RESULTS
  The graft rs2735940 hTERT gene polymorphism TT genotype was associated with a significantly lower risk of delayed graft function (DGF) (TT vs. TC+CC; OR=0, p=0.009) and significantly shorter TL in the '0' biopsy (TT vs. CC: 207±153 vs. 400±161, p=0.036). The graft rs2630578 BICD1 gene polymorphism CC genotype was associated with lower creatinine concentrations in the first month (CC vs. GC: 1.11±0.06 vs. 2.0±1.25 mg/dL, p=0.03). The AA genotype of the graft rs7235755 chromosome 18 polymorphism was associated with longer relative TL in specimens collected 12 to 60 months after transplantation (AA vs. GG+GA p=0.04; AA vs. GG: 489±152 vs. 246±145, p=0.035) and the presence of A allele was associated with higher creatinine concentrations one month after transplantation (GA+AA vs. GG p=0.026; GA vs. GG: 2.18±1.59 vs. 1.76±0.88 mg/dL, p=0.02). It was found that shorter TL in the first six months was associated with higher creatinine concentrations 12 and 18 months after transplantation (Rs=-0.32; p=0.07 and Rs=-0.54; p=0.006, respectively).
  
  
  CONCLUSIONS
  Graft rs2735940 hTERT and rs2630578 BICD1 gene polymorphisms and rs7235755/rs2162440 chromosome 18 polymorphisms, apart from the association with TL, affect early kidney function after transplantation. Relative TL correlated negatively with creatinine concentrations, allowing the use of TL as a predictor of long-term kidney function.
authors: Clinical Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin, Poland.
authors: Karolina
authors: K
authors: Kłoda
authors: Leszek
authors: L
authors: Domanski
authors: Ewa
authors: E
authors: Kwiatkowska
authors: Ewa
authors: E
authors: Borowiecka
authors: Krzysztof
authors: K
authors: Safranow
authors: Arleta
authors: A
authors: Drozd
authors: Andrzej
authors: A
authors: Ciechanowicz
authors: Agnieszka
authors: A
authors: Maciejewska-Karłowska
authors: Marek
authors: M
authors: Sawczuk
authors: Andrzej
authors: A
authors: Pawlik
authors: Kazimierz
authors: K
authors: Ciechanowski
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D003404:Creatinine / Q000097:blood; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D006084:Graft Rejection / Q000235:genetics; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011044:Poland; D011110:Polymorphism, Genetic / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000235:genetics*; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C109571:BICD1 protein, human; D003598:Cytoskeletal Proteins; D004247:DNA; D003404:Creatinine; C509186:TERT protein, human; D019098:Telomerase