Leiherer Andreas, Muendlein Axel, Rein Philipp, Saely Christoph H, Kinz Elena, Vonbank Alexander, Fraunberger Peter, Drexel Heinz
Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein; Medical Central Laboratories, Feldkirch, Austria.
Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria.
PLoS One. 2014 Dec 5;9(12):e114240. doi: 10.1371/journal.pone.0114240. eCollection 2014.
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.
肾功能受损是一个重大的健康问题,也是临床日常工作中的主要关注点,通常通过肾小球滤过率(GFR)降低来确定。与仅提供有限患者健康信息的单次肾功能评估相比,GFR的系列测量明显提高了诊断的有效性。最近有报道称,肾功能下降可预测冠心病患者的死亡率和血管事件。然而,在全基因组关联研究(GWA研究)中尚未对其进行基因关联研究。本研究首次使用心脏代谢芯片,调查了583例冠心病患者在4年随访期间心脏代谢多态性与估计GFR下降之间的关联。我们发现了3种多态性的提示性关联,超过了全基因组显著性水平(p = 4.0×10⁻⁷)。最显著的rs17069906(p = 5.6×10⁻¹⁰)位于RANK基因区域内,最近已证明其在足细胞适应性恢复反应中起重要作用,并被认为是肾小球疾病中有前景的治疗靶点。