BICD1 and Chromosome 18 Polymorphisms Associated With Recipients' Telomere Length Affect Kidney Allograft Function After Transplantation

Transplant Proc. 2016 Jun;48(5):1451-5. doi: 10.1016/j.transproceed.2015.10.086.

Abstract

Background: Reports regarding recipient's nonmodifiable genetic factors affecting telomerase activity and thus allograft function are lacking. Therefore the aim of this study was to analyze the associations between recipients' rs2735940 hTERT, rs2630578 BICD1, and rs7235755 chromosome 18 polymorphisms and kidney function after transplantation.

Methods: The study enrolled 119 white Polish kidney allograft recipients (64 men, 55 women; overall mean age, 47.3 ± 14.0 y). To identify genotypes of the studied polymorphisms, real-time polymerase chain reaction was performed.

Results: There were statistically significant differences in distribution of rs7235755 chromosome 18 polymorphism genotypes and alleles between recipients with delayed graft function (DGF) and without DGF (P = .03). The presence of A allele was significantly associated with higher risk of DGF occurrence (AA + GA vs GG: OR, 3.25 [95% CI, 1.16-9.14]; P = .02; GA vs GG: OR, 4.00 [1.35-11.82]; P = .01). Analysis of the rs2630578 BICD1 gene polymorphism genotypes revealed statistically significant differences in long-term creatinine concentrations. The presence of C allele of this polymorphism was significantly associated with higher creatinine concentrations 24, 36, and 18-48 months after transplantation (GC + CC vs GG: P = .008, P = .008, and P = .01, respectively).

Conclusions: Recipients' polymorphisms of genes associated with telomere length, BICD1 and chromosome 18, but not hTERT, affect kidney allograft early and long-term function after transplantation. There is an urgent need for explanation of these observations in genome-wide association studies.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Alleles
  • Allografts / physiopathology*
  • Chromosomes, Human, Pair 18 / genetics*
  • Creatinine / blood
  • Cytoskeletal Proteins / genetics*
  • Delayed Graft Function / genetics*
  • Female
  • Genotype
  • Humans
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Poland
  • Polymorphism, Genetic
  • Real-Time Polymerase Chain Reaction
  • Telomerase / genetics
  • Telomere

Substances

  • Adaptor Proteins, Signal Transducing
  • BICD1 protein, human
  • Cytoskeletal Proteins
  • Creatinine
  • Telomerase