Common variants in UMOD associate with urinary uromodulin levels: A meta-analysis

Matthias Olden, Tanguy Corre, Caroline Hayward, Daniela Toniolo, Sheila Ulivi, Paolo Gasparini, Giorgio Pistis, Shih Jen Hwang, Sven Bergmann, Harry Campbell, Massimiliano Cocca, Ilaria Gandin, Giorgia Girotto, Bob Glaudemans, Nicholas D. Hastie, Johannes Loffing, Ozren Polasek, Luca Rampoldi, Igor Rudan, Cinzia SalaMichela Traglia, Peter Vollenweider, Dragana Vuckovic, Sonia Youhanna, Julien Weber, Alan F. Wright, Zoltán Kutalik, Murielle Bochud, Caroline S. Fox, Olivier Devuyst

Research output: Contribution to journalArticlepeer-review

Abstract

Uromodulin is expressed exclusively in the thick ascending limb and is the most abundant protein excreted in normal urine. Variants in UMOD, which encodes uromodulin, are associated with renal function, and urinary uromodulin levels may be a biomarker for kidney disease. However, the genetic factors regulating uromodulin excretion are unknown.We conducted ameta-analysis of urinary uromodulin levels to identify associatedcommon genetic variants in the general population.We included10,884 individuals of European descent from three genetic isolates and three urban cohorts. Each study measured uromodulin indexed to creatinine and conducted linear regression analysis of approximately 2.5 million single nucleotide polymorphisms using an additive model.Wealso tested whether variants in genes expressed in the thick ascending limb associate with uromodulin levels. rs12917707, located near UMOD and previously associated with renal function and CKD, had the strongest association with urinary uromodulin levels (P

Original languageEnglish
Pages (from-to)1869-1882
Number of pages14
JournalJournal of the American Society of Nephrology
Volume25
Issue number8
DOIs
Publication statusPublished - Aug 1 2014

ASJC Scopus subject areas

  • Nephrology
  • Medicine(all)

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