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

Details

Serval ID
serval:BIB_AEA01CA5EB11
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Common variants in CLDN14 are associated with differential excretion of magnesium over calcium in urine.
Journal
Pflugers Archiv
Author(s)
Corre T., Olinger E., Harris S.E., Traglia M., Ulivi S., Lenarduzzi S., Belge H., Youhanna S., Tokonami N., Bonny O., Houillier P., Polasek O., Deary I.J., Starr J.M., Toniolo D., Gasparini P., Vollenweider P., Hayward C., Bochud M., Devuyst O.
ISSN
1432-2013 (Electronic)
ISSN-L
0031-6768
Publication state
Published
Issued date
01/2017
Peer-reviewed
Oui
Volume
469
Number
1
Pages
91-103
Language
english
Notes
Publication types: Journal Article ; Review
Publication Status: ppublish
Review changed to Article by Bibliomics (AP)
Abstract
The nature and importance of genetic factors regulating the differential handling of Ca(2+) and Mg(2+) 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 Mg(2+) over Ca(2+) 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.

Keywords
Animals, Calcium/metabolism, Calcium/urine, Claudins/genetics, Humans, Kidney Tubules/metabolism, Magnesium/metabolism, Magnesium/urine, Polymorphism, Single Nucleotide/genetics, Urine/chemistry, Claudin-14, GWAS, Mg/Ca ratio, Tubular functions
Pubmed
Web of science
Create date
12/12/2016 19:43
Last modification date
20/08/2019 15:18
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