Role of TGF-β1 +869T>C polymorphism in renal dysfunction one year after heart transplantation

J Heart Lung Transplant. 2022 Dec;41(12):1672-1678. doi: 10.1016/j.healun.2022.09.004. Epub 2022 Sep 15.

Abstract

Background: Chronic kidney disease is a major complication after heart transplantation with wide inter-individual variability. Calcineurin inhibitor nephrotoxicity, mediated by transforming growth factor-beta1 (TGF-β1), is an important contributing factor. Our objective was to evaluate the association between TGF-β1 polymorphisms and renal dysfunction 1-year after heart transplantation.

Methods: Single-center observational study that included patients who received a first heart transplant between 1990-2013. According to the 1-year eGFR decline, patients were classified as "Stable" (decrease in eGFR<10% or eGFR>60 ml/min/1.73m2) or "Progressors" (decrease in eGFR>10% and eGFR<60 ml/min/1.73m2). "Progressors" were then subdivided by the degree of eGFR decrease in "Mild progressors" (10-30%) or "Rapid progressors" (>30%). The association between TGF-β1 +869T>C polymorphism and other risk factors with the eGFR outcome was analysed.

Results: A total of 355 patients (78% male; 50.7 ± 11.8 years) were included. According to the 1-year eGFR decline, 220 patients (62%) were classified as "Stable" and 135 (38%) as "Progressors". TGF-β1+869CC genotype was more prevalent in "Stable" vs "Progressors" group (20% vs 8%, p = 0.009). In the multivariate analysis, female sex (p 0.02) and eGFR<60 ml/min/1.73 m2 at first month post-heart transplant (p = 0.004) remained as risk factors of eGFR decline, and TGF-β1 + 869CC genotype (p = 0.001) and renal dysfunction pre-heart transplant (p = 0.04) as protective factors. TGF-β1 + 869CC genotype was less frequently found in "Mild progressors" compared to "Rapid progressors" [p = 0.019; OR (95%CI) = 0.19 (.05-.76)].

Conclusions: The TGF-β1 +869CC genotype is associated with a lower risk of calcineurin inhibitor nephrotoxicity after heart transplant. This genetic susceptibility could enable a more personalized patient treatment.

Keywords: calcineurion inhibitor; crhonic kidney disease; heart transplantation; polymorphism; transforming growth factor.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Calcineurin Inhibitors
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Heart Transplantation*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Renal Insufficiency, Chronic* / genetics
  • Transforming Growth Factor beta1* / genetics

Substances

  • Calcineurin Inhibitors
  • Transforming Growth Factor beta1
  • TGFB1 protein, human