1. Genetic markers associated with long-term cardiovascular outcome in kidney transplant recipients.
- Author
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Pihlstrøm HK, Mjøen G, Mucha S, Franke A, Jardine A, Fellström B, Dahle DO, Holdaas H, and Melum E
- Subjects
- Adult, Aged, Cardiovascular Diseases etiology, Cardiovascular Diseases metabolism, Double-Blind Method, Female, Follow-Up Studies, Genome-Wide Association Study, Glomerular Filtration Rate, Graft Rejection etiology, Graft Rejection metabolism, Graft Survival, Humans, Kidney Function Tests, Male, Middle Aged, Prognosis, Risk Factors, Cardiovascular Diseases diagnosis, Genetic Markers, Graft Rejection diagnosis, Kidney Failure, Chronic surgery, Kidney Transplantation adverse effects, Polymorphism, Single Nucleotide, Postoperative Complications
- 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., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2019
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