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

Schmitz B, Kleber ME, Lenders M, Delgado GE, Engelbertz C, Huang J, Pavenstaedt H, Breithardt G, Brand S, Maerz W, Brand E

Abstract

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 m(2). 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 x 10(-9), mean eGFR 60.7 ml/min/1.73 m(2)). Direct genotyping of rs139401390A > G suggested increased eGFR by 12.0 ml/min/1.73 m(2) 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 m(2) (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 < 60 ml/min/1.73 m(2) for CAD patients (n = 1992, OR = 2.36, p = 0.008, G/A + G/G vs A/A) compared to patients with/without CAD (n = 2908, OR = 1.97, p = 0.014, G/A + G/G vs A/A). No significant risk elevation was detected in patients without CAD (n = 948, p = 0.571). rs139401390 may affect kidney function in CAD patients with mild reduction in eGFR.