Genome-wide association study suggests impact of chromosome 10 rs139401390 on kidney function in patients with coronary artery disease

Chronic kidney disease (CKD) is an independent risk factor for onset and progression of coronary artery disease (CAD). Discovery of predisposing loci for kidney function in CAD patients was performed using a genome-wide association approach. Inclusion criteria were CAD with ≥50% stenosis (≥1 coronar...

Authors: Schmitz, Boris
Kleber, Marcus E.
Lenders, Malte
Delgado Gonzales de Kleber, Graciela
Engelbertz, Christiane Maria
Huang, Jie
Pavenstädt, Hermann
Breithardt, Günter
Brand, Stefan-Martin
März, Winfried
Brand, Eva
Division/Institute:FB 13: Biologie
FB 05: Medizinische Fakultät
Document types:Article
Media types:Text
Publication date:2019
Date of publication on miami:22.08.2019
Modification date:22.08.2019
Edition statement:[Electronic ed.]
Source:Scientific Reports 9 (2019) 2750, 1-8
DDC Subject:610: Medizin und Gesundheit
License:CC BY 4.0
Language:English
Funding:Finanziert durch den Open-Access-Publikationsfonds 2018 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format:PDF document
URN:urn:nbn:de:hbz:6-04109514654
Permalink:http://nbn-resolving.de/urn:nbn:de:hbz:6-04109514654
Other Identifiers:DOI: 10.1038/s41598-019-39055-y
Digital documents:artikel_brand_2019.pdf

Chronic kidney disease (CKD) is an independent risk factor for onset and progression of coronary artery disease (CAD). Discovery of predisposing loci for kidney function in CAD patients was performed using a genome-wide association approach. Inclusion criteria were CAD with ≥50% stenosis (≥1 coronary artery) and a creatinine-based estimated glomerular filtration rate (eGFR) of 30–75 ml/min/1.73 m2. An association of rs139401390 located to a region 58.8 kb upstream of renalase (RNLS) with eGFR was detected in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study (n = 499, p = 7.88 × 10−9, mean eGFR 60.7 ml/min/1.73 m2). Direct genotyping of rs139401390A > G suggested increased eGFR by 12.0 ml/min/1.73 m2 per A allele (p = 0.000004). Genome-wide replication of rs139401390A > G in the Coronary Artery Disease and Renal Failure (CAD-REF) registry with a mean eGFR of 47.8 ml/min/1.73 m2 (n = 574, p = 0.033) was only nominally significant. Comparison of rs139401390 genotypes for risk of reduced kidney function in the overall LURIC study revealed higher adjusted odds ratios (OR) for eGFR