Back
Common variants in CLDN14 are associated with differential excretion of magnesium over calcium in urine.
Journal article

Common variants in CLDN14 are associated with differential excretion of magnesium over calcium in urine.

  • Corre T Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.
  • Olinger E Institute of Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland.
  • Harris SE Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
  • Traglia M Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
  • Ulivi S Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, Italy.
  • Lenarduzzi S Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, Italy.
  • Belge H Institute of Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland.
  • Youhanna S Institute of Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland.
  • Tokonami N Institute of Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland.
  • Bonny O Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
  • Houillier P INSERM U1138, Centre de Recherche des Cordeliers, Paris, France.
  • Polasek O Faculty of Medicine, University of Split, Split, Croatia.
  • Deary IJ Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
  • Starr JM Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
  • Toniolo D Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
  • Gasparini P Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
  • Vollenweider P Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
  • Hayward C MRC IGMM, University of Edinburgh, Edinburgh, UK.
  • Bochud M Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.
  • Devuyst O Institute of Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland. olivier.devuyst@uzh.ch.
Show more…
  • 2016-12-05
Published in:
  • Pflugers Archiv : European journal of physiology. - 2017
Claudin-14
GWAS
Mg/Ca ratio
Tubular functions
Animals
Calcium
Claudins
Humans
Kidney Tubules
Magnesium
Polymorphism, Single Nucleotide
Urine
English The nature and importance of genetic factors regulating the differential handling of Ca2+ and Mg2+ by the renal tubule in the general population are poorly defined. We conducted a genome-wide meta-analysis of urinary magnesium-to-calcium ratio to identify associated common genetic variants. We included 9320 adults of European descent from four genetic isolates and three urban cohorts. Urinary magnesium and calcium concentrations were measured centrally in spot urine, and each study conducted linear regression analysis of urinary magnesium-to-calcium ratio on ~2.5 million single-nucleotide polymorphisms (SNPs) using an additive model. We investigated, in mouse, the renal expression profile of the top candidate gene and its variation upon changes in dietary magnesium. The genome-wide analysis evidenced a top locus (rs172639, p = 1.7 × 10-12), encompassing CLDN14, the gene coding for claudin-14, that was genome-wide significant when using urinary magnesium-to-calcium ratio, but not either one taken separately. In mouse, claudin-14 is expressed in the distal nephron segments specifically handling magnesium, and its expression is regulated by chronic changes in dietary magnesium content. A genome-wide approach identified common variants in the CLDN14 gene exerting a robust influence on the differential excretion of Mg2+ over Ca2+ in urine. These data highlight the power of urinary electrolyte ratios to unravel genetic determinants of renal tubular function. Coupled with mouse experiments, these results support a major role for claudin-14, a gene associated with kidney stones, in the differential paracellular handling of divalent cations by the renal tubule.
Language
  • English
Open access status
green
Identifiers
Persistent URL
https://sonar.ch/global/documents/47361
Statistics
Document views: 17 File downloads: