Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA.
Nat Genet. 2009 Jun;41(6):712-7. doi: 10.1038/ng.377. Epub 2009 May 10.
Chronic kidney disease (CKD) has a heritable component and is an important global public health problem because of its high prevalence and morbidity. We conducted genome-wide association studies (GWAS) to identify susceptibility loci for glomerular filtration rate, estimated by serum creatinine (eGFRcrea) and cystatin C (eGFRcys), and CKD (eGFRcrea < 60 ml/min/1.73 m(2)) in European-ancestry participants of four population-based cohorts (ARIC, CHS, FHS, RS; n = 19,877; 2,388 CKD cases), and tested for replication in 21,466 participants (1,932 CKD cases). We identified significant SNP associations (P < 5 × 10(-8)) with CKD at the UMOD locus, with eGFRcrea at UMOD, SHROOM3 and GATM-SPATA5L1, and with eGFRcys at CST and STC1. UMOD encodes the most common protein in human urine, Tamm-Horsfall protein, and rare mutations in UMOD cause mendelian forms of kidney disease. Our findings provide new insights into CKD pathogenesis and underscore the importance of common genetic variants influencing renal function and disease.
慢性肾脏病（CKD）具有遗传成分，是一个重要的全球公共卫生问题，因为其发病率和患病率都很高。我们进行了全基因组关联研究（GWAS），以鉴定肾小球滤过率（通过血清肌酐[eGFRcrea]和胱抑素 C[eGFRcys]估计）和 CKD（eGFRcrea < 60 ml/min/1.73 m(2)）的易感基因座，这些研究是在四个基于人群的队列（ARIC、CHS、FHS、RS；n = 19,877；2,388 例 CKD 病例）中的欧洲血统参与者中进行的，并在 21,466 名参与者（1,932 例 CKD 病例）中进行了复制检验。我们在 UMOD 基因座、eGFRcrea 基因座的 UMOD、SHROOM3 和 GATM-SPATA5L1、eGFRcys 基因座的 CST 和 STC1 上发现了与 CKD 显著相关的 SNP 关联（P < 5 × 10(-8)）。UMOD 编码人尿中最常见的蛋白质，Tamm-Horsfall 蛋白，而 UMOD 的罕见突变会导致肾脏疾病的孟德尔形式。我们的研究结果为 CKD 的发病机制提供了新的见解，并强调了影响肾功能和疾病的常见遗传变异的重要性。
