<b><i>hTERT, BICD1</i></b> and Chromosome 18 Polymorphisms Associated with Telomere Length Affect Kidney Allograft Function After Transplantation

Abstract

Background/Aims: 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.

Joint Assessment of Donor and Recipient hTERT Gene Polymorphism Provides Additional Information for Early Kidney Transplantation Outcomes

“…The frequencies of rs2735940 hTERT gene and rs2630578 BICD1 gene polymorphisms, as well as rs7235755 within chromosome 18 polymorphisms, among the recipients and donors were consistent with the Hardy-Weinberg equilibrium. These results have been described elsewhere [9,12]. …”

“…It is broadly known that among them, genetic factors are of great importance [9,12,23]. There are also many promising studies focused on linkage between immune response mediators and cell status.…”

“…Primarily hTERT gene, BICD1 gene, and polymorphisms within chromosome 18 alter telomere shortening [9]. These age-related findings are especially important in kidney transplantation, because it has been demonstrated that the age of the donor is a negative factor associated with long-term kidney allograft function, and post-transplant complications accelerate transplanted organ aging thus contributing to decreases in eGFR [10,11].…”

Telomere Length Assessment for Prediction of Organ Transplantation Outcome. Future or Failure: A Review of the Literature

“…Currently, this term has been replaced with chronic allograft dysfunction (CAD), which is a much broader definition of long-term transplanted kidney function impairment. The diagnosis of CAD is based on functional and morphological (biopsy confirmed) deterioration of renal allograft at least 3–6 months after transplantation, whereas diagnosis of CAN was based on tissue examination [23–25]. Ferlicot et al studied 67 cases of CAN and 13 controls.…”

“…In the case of the rs7235755 chromosome 18 polymorphism AA genotype, significant correlations were found, but they differed depending on the time of material collection. Nevertheless, we showed that genetic factors also influence telomere length and must be considered in further studies [25]. …”