Genome-wide association study reveals a polymorphism in the podocyte receptor RANK for the decline of renal function in coronary patients

• Published in: PloS one 2014-12, Vol.9 (12), p.e114240-e114240
• Main Authors: Leiherer, Andreas, Muendlein, Axel, Rein, Philipp, Saely, Christoph H, Kinz, Elena, Vonbank, Alexander, Fraunberger, Peter, Drexel, Heinz
• Format: Article
• Language: English
• Subjects: Aged; Atherosclerosis; Biology and Life Sciences; Calcification; Cardiology; Cardiovascular disease; Coronary Artery Disease - complications; Coronary Artery Disease - genetics; Coronary Artery Disease - pathology; Coronary vessels; Diabetes; Female; Genetic aspects; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Glomerular Filtration Rate; Health aspects; Humans; Kidney diseases; Kidney Diseases - etiology; Kidney Diseases - genetics; Kidney Diseases - pathology; Kidneys; Laboratories; Male; Medical imaging; Medicine; Medicine and Health Sciences; Metabolism; Metabolites; Middle Aged; Patients; Podocytes - pathology; Polymorphism; Polymorphism, Single Nucleotide; Population; Private schools; Receptor Activator of Nuclear Factor-kappa B - genetics; Renal function; Research and Analysis Methods; Risk Factors; Studies; Therapeutic applications
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0114240

Impaired kidney function is a significant health problem and a major concern in clinical routine and is routinely determined by decreased glomerular filtration rate (GFR). In contrast to single assessment of a patients' kidney function providing only limited information on patients' health, serial measurements of GFR clearly improves the validity of diagnosis. The decline of kidney function has recently been reported to be predictive for mortality and vascular events in coronary patients. However, it has not been investigated for genetic association in GWA studies. This study investigates for the first time the association of cardiometabolic polymorphisms with the decline of estimated GFR during a 4 year follow up in 583 coronary patients, using the Cardio-Metabo Chip. We revealed a suggestive association with 3 polymorphisms, surpassing genome-wide significance (p = 4.0 e-7). The top hit rs17069906 (p = 5.6 e-10) is located within the genomic region of RANK, recently demonstrated to be an important player in the adaptive recovery response in podocytes and suggested as a promising therapeutic target in glomerular diseases.