title: High plasma chemerin is associated with renal dysfunction and predictive for cardiovascular events - Insights from phenotype and genotype characterization.
abstract: The novel adipokine chemerin, encoded by the RARRES2 gene, has been suggested to be linked to insulin resistance and to the metabolic syndrome (MetS). However, no well-defined cardiovascular profile has been reported and the association with coronary artery disease (CAD) is a matter of debate. Because there is a relation between renal dysfunction and CAD, we analyzed plasma chemerin levels and the estimated glomerular filtration rate (eGFR) in 495 patients undergoing coronary angiography for the evaluation of established or suspected stable CAD. Chemerin levels were higher in patients with Type 2 diabetes mellitus (T2DM, n=111) and the metabolic syndrome (MetS, n=147) than in subjects without T2DM (191.5±72.9 vs. 169.7±64.7ng/ml, p=0.001) or the MetS (201.2±71.0 vs. 163,1ng/ml, p<0.001), but did not differ significantly between patients with significant CAD (n=247) and those without significant CAD (177.1±67.0 vs. 171.7±67.2ng/ml, p=0.193). Analysis of covariance using age, sex, and BMI as covariates showed that chemerin was significantly and independently associated with eGFR (F=49.6, p<0.001). After an 8-year follow-up period, patients with high chemerin levels were more often affected by cardiovascular events (HR=1.72 [95% CI 1.19-2.47], p=0.004), even after appropriate adjustment for age, gender, BMI, as well as eGFR (adjusted HR 1.51 [95% CI 1.03-2.23], p=0.037). Given the cardiometabolic role of chemerin, we also applied a Cardio-Metabo Chip analysis and revealed a genome-wide significant association with SNPs (rs55709438, rs2444030, and rs3098423) located at chromosomal region 15q15-23, which were associated with metabolic traits and eGFR. This study for the first time demonstrates that high chemerin concentrations are significantly associated with renal impairment and predictive of cardiovascular events and that 15q15-23 might have an impact on chemerin levels beyond common genetic variations in RARRES2.
authors: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein; Medical Central Laboratories, Feldkirch, Austria.
authors: Andreas
authors: A
authors: Leiherer
authors: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.
authors: Axel
authors: A
authors: Muendlein
authors: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.
authors: Elena
authors: E
authors: Kinz
authors: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.
authors: Alexander
authors: A
authors: Vonbank
authors: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.
authors: Philipp
authors: P
authors: Rein
authors: Private University of the Principality of Liechtenstein, Triesen, Liechtenstein; Medical Central Laboratories, Feldkirch, Austria.
authors: Peter
authors: P
authors: Fraunberger
authors: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.
authors: Cornelia
authors: C
authors: Malin
authors: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.
authors: Christoph H
authors: CH
authors: Saely
authors: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein; Drexel University College of Medicine, Philadelphia, PA, USA. Electronic address: vivit@lkhf.at.
authors: Heinz
authors: H
authors: Drexel
mesh_terms: D000368:Aged; D018925:Chemokines / Q000097:blood* / Q000235:genetics; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000097:blood* / Q000235:genetics / Q000401:mortality / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D018450:Disease Progression; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D005919:Glomerular Filtration Rate; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000235:genetics / Q000401:mortality / Q000503:physiopathology
chemical_list: D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; C478630:RARRES2 protein, human
keywords: Adipokine; Cardio-Metabo Chip; Chemerin; Coronary artery disease; Renal dysfunction