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Genetic markers associated with long‐term cardiovascular outcome in kidney transplant recipients
Author(s) -
Pihlstrøm Hege K.,
Mjøen Geir,
Mucha Sören,
Franke Andre,
Jardine Alan,
Fellström Bengt,
Dahle Dag Olav,
Holdaas Hallvard,
Melum Espen
Publication year - 2019
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.15191
Subject(s) - medicine , hazard ratio , population , kidney transplantation , single nucleotide polymorphism , proportional hazards model , odds ratio , transplantation , mace , confidence interval , genotype , myocardial infarction , genetics , biology , percutaneous coronary intervention , environmental health , gene
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 ( SNP s) 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 SNP s 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.