Association of Estimated Glomerular Filtration Rate and Urinary Uromodulin Concentrations with Rare Variants Identified by UMOD Gene Region Sequencing
Association of Estimated Glomerular Filtration Rate and Urinary Uromodulin Concentrations with Rare Variants Identified by UMOD Gene Region Sequencing
复制标题
估计肾小球滤过率和尿液中尿嘧啶浓度与 UMOD 基因区域测序发现的罕见变异的关系
DOI：
10.1371/journal.pone.0038311
复制
发表时间：
2012-05-31
期刊：
影响因子：
3.7
通讯作者：
Fox, Caroline S.
中科院分区：
文献类型：
--
作者：
Koettgen, Anna;Yang, Qiong;Fox, Caroline S.
背景：最近的全基因组关联研究发现，在普通人群中，UMOD区域的常见变异与肾功能和疾病有关。方法/主要研究结果：根据ARIC研究中Gwas风险单倍型和慢性肾脏疾病(CKD)的存在以及Framingham心脏研究(FHS)中UMOD基因产物尿调蛋白(THP)的极端情况，选择了485名个体。使用基于毛细管的Sanger测序(3730DNA分析仪)进行靶向测序。我们测试了变异与THP浓度和估计的肾小球滤过率(EGFR)的相关性，并在多达22,546个随访样本中对识别出的非同义编码变异进行了基因分型。在285名ARIC和200名FHS参与者中，分别发现了24 63个变异。在这两项研究中，共有33例常见病例和54例罕见病例(MAF
Background: Recent genome-wide association studies (GWAS) have identified common variants in the UMOD region associated with kidney function and disease in the general population. To identify novel rare variants as well as common variants that may account for this GWAS signal, the exons and 4 kb upstream region of UMOD were sequenced.Methodology/Principal Findings: Individuals (n = 485) were selected based on presence of the GWAS risk haplotype and chronic kidney disease (CKD) in the ARIC Study and on the extremes of of the UMOD gene product, uromodulin, in urine (Tamm Horsfall protein, THP) in the Framingham Heart Study (FHS). Targeted sequencing was conducted using capillary based Sanger sequencing (3730 DNA Analyzer). Variants were tested for association with THP concentrations and estimated glomerular filtration rate (eGFR), and identified non-synonymous coding variants were genotyped in up to 22,546 follow-up samples. Twenty-four and 63 variants were identified in the 285 ARIC and 200 FHS participants, respectively. In both studies combined, there were 33 common and 54 rare (MAF