Genetic markers associated with long-term cardiovascular outcome in kidney transplant recipients

Am J Transplant. 2019 May;19(5):1444-1451. doi: 10.1111/ajt.15191. Epub 2018 Dec 18.

Abstract

There is a clear genetic contribution to the risk of cardiovascular diseases, and a composite genetic risk score (GRS) based on 27 single nucleotide polymorphisms (SNPs) was reported to predict risk of cardiovascular events in the general population. We aimed to evaluate this risk score in renal transplant recipients, a population with heightened cardiovascular risk, with a yet unknown genetic contribution. A total of 1640 participants from the ALERT trial (Assessment of Lescol in Renal Transplantation), a study comparing fluvastatin with placebo in stable renal transplant recipients, were genotyped for all SNPs making up the GRS. Risk alleles were weighted by the log of odds ratios reported in genome wide association studies and summed. Associations between GRS and time from study inclusion to first major cardiovascular event (MACE) were analyzed by Cox regression. In analyses adjusted for cardiovascular risk factors, GRS was significantly associated with MACE (hazard ratio [HR] 1.81, P = .006) when comparing genetic high-risk patients (quartile 4) with genetic low-risk participants (quartile 1). A 27-SNP GRS, which predicted cardiovascular events in the nontransplant population, appears to have predictive value also in kidney allograft recipients. Refining the score to better fit the transplant population seems feasible.

Keywords: biomarker; clinical research/practice; coronary artery disease; epidemiology; genetics; kidney transplantation/nephrology; risk assessment/risk stratification; translational research/science.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cardiovascular Diseases / diagnosis*
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / metabolism
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Genetic Markers*
  • Genome-Wide Association Study
  • Glomerular Filtration Rate
  • Graft Rejection / diagnosis*
  • Graft Rejection / etiology
  • Graft Rejection / metabolism
  • Graft Survival
  • Humans
  • Kidney Failure, Chronic / surgery*
  • Kidney Function Tests
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Postoperative Complications*
  • Prognosis
  • Risk Factors

Substances

  • Genetic Markers