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肾脏病学中的整合基因组学与代谢组学

Integrated genomics and metabolomics in nephrology.

作者信息

Atzler Dorothee, Schwedhelm Edzard, Zeller Tanja

机构信息

Department of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany German Center for Cardiovascular Research (DZHK), Partner Side Hamburg/Lübeck/Kiel.

German Center for Cardiovascular Research (DZHK), Partner Side Hamburg/Lübeck/Kiel Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.

出版信息

Nephrol Dial Transplant. 2014 Aug;29(8):1467-74. doi: 10.1093/ndt/gft492. Epub 2013 Dec 22.

Abstract

Applying 'omics' approaches such as genome-wide association studies (GWAS) and metabolome analyses, genes and metabolites have been identified to be associated with renal pathophysiology. Meta-analyses of GWAS from large epidemiologic cohorts uncovered several novel loci linked with estimated glomerular filtration rate and chronic kidney disease (CKD). Sophisticated analytical technologies, including mass spectrometry and nuclear magnetic resonance spectroscopy, allow the analyses of up to 4000 targeted and non-targeted metabolites in plasma, serum and urine. Several uraemic toxins were found that were increased in CKD. Among them, arginine derivatives like asymmetric dimethylarginine or tryptophane metabolites have been identified as promising candidates to target mechanisms of kidney disease progression. This review aims to summarize recent findings in clinical kidney diseases research revealed by 'omics' approaches with a clear focus on recent genomics and metabolomics efforts.

摘要

应用全基因组关联研究(GWAS)和代谢组分析等“组学”方法,已确定基因和代谢物与肾脏病理生理学相关。对大型流行病学队列的GWAS进行的荟萃分析发现了几个与估计肾小球滤过率和慢性肾脏病(CKD)相关的新位点。先进的分析技术,包括质谱和核磁共振波谱,可对血浆、血清和尿液中的多达4000种靶向和非靶向代谢物进行分析。发现了几种在CKD中增加的尿毒症毒素。其中,不对称二甲基精氨酸等精氨酸衍生物或色氨酸代谢物已被确定为针对肾脏疾病进展机制的有前景的候选物。本综述旨在总结“组学”方法在临床肾脏疾病研究中的最新发现,特别关注近期的基因组学和代谢组学研究成果。

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