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

Andreas Leiherer; Axel Muendlein; Philipp Rein; Christoph H Saely; Elena Kinz; Alexander Vonbank; Peter Fraunberger; Heinz Drexel

doi:10.1371/journal.pone.0114240

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

PLoS One. 2014 Dec 5;9(12):e114240. doi: 10.1371/journal.pone.0114240. eCollection 2014.

Authors

Andreas Leiherer¹, Axel Muendlein², Philipp Rein³, Christoph H Saely⁴, Elena Kinz⁵, Alexander Vonbank³, Peter Fraunberger⁶, Heinz Drexel⁷

Affiliations

¹ Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein; Medical Central Laboratories, Feldkirch, Austria.
² Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria.
³ Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.
⁴ 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.
⁵ Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.
⁶ Private University of the Principality of Liechtenstein, Triesen, Liechtenstein; Medical Central Laboratories, Feldkirch, Austria.
⁷ 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, United States of America.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Coronary Artery Disease / complications
Coronary Artery Disease / genetics*
Coronary Artery Disease / pathology
Female
Genome-Wide Association Study*
Glomerular Filtration Rate
Humans
Kidney Diseases / etiology
Kidney Diseases / genetics*
Kidney Diseases / pathology
Male
Middle Aged
Podocytes / pathology
Polymorphism, Single Nucleotide
Receptor Activator of Nuclear Factor-kappa B / genetics*
Risk Factors

Substances

Receptor Activator of Nuclear Factor-kappa B
TNFRSF11A protein, human

Grants and funding

This study was supported by grants from the "Land Vorarlberg" and the "College of Physicians in Vorarlberg", but the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.