User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

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

Primary tabs

Corre, Tanguy Olinger, Eric Harris, Sarah E Traglia, Michela Ulivi, Sheila Belge, Hendrica [UCL] Devuyst, Olivier [UCL]

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.

Document type Article de périodique (Journal article) – Synthèse de littérature
Access type Accès interdit
Publication date 2017
Language Anglais
Journal information "Pflügers Archiv - European journal of physiology" - Vol. 469, no. 1, p. 91-103 (2017)
Peer reviewed yes
Publisher Springer ((Germany) Berlin)
issn 0031-6768
e-issn 1432-2013
Publication status Publié
Affiliations UCL - SSS/IREC/NEFR - Pôle de Néphrologie
UCL - (SLuc) Service de néphrologie
Keywords Claudin-14 ; GWAS ; Mg/Ca ratio ; Tubular functions
Links
  1. Ben-Yosef T., Claudin 14 knockout mice, a model for autosomal recessive deafness DFNB29, are deaf due to cochlear hair cell degeneration, 10.1093/hmg/ddg210
  2. Blanchard Anne, Jeunemaitre Xavier, Coudol Philippe, Dechaux Michèle, Froissart Marc, May Adrien, Demontis Renato, Fournier Albert, Paillard Michel, Houillier Pascal, Paracellin-1 is critical for magnesium and calcium reabsorption in the human thick ascending limb of Henle, 10.1046/j.1523-1755.2001.0590062206.x
  3. Bleich Markus, Shan Qixian, Himmerkus Nina, Calcium regulation of tight junction permeability : Calcium regulation of tight junction permeability, 10.1111/j.1749-6632.2012.06539.x
  4. Bonny O., Rubin A., Huang C.-L., Frawley W. H., Pak C. Y.C., Moe O. W., Mechanism of Urinary Calcium Regulation by Urinary Magnesium and pH, 10.1681/asn.2007091038
  5. Bushinsky DA, Favus MJ, Langman CB, Coe FL (1986) Mechanism of chronic hypercalciuria with furosemide: increased calcium absorption. Am J Phys 251:F17–F24
  6. de Baaij J. H. F., Hoenderop J. G. J., Bindels R. J. M., Magnesium in Man: Implications for Health and Disease, 10.1152/physrev.00012.2014
  7. de Groot Theun, Bindels René J.M., Hoenderop Joost G.J., TRPV5: an ingeniously controlled calcium channel, 10.1038/ki.2008.320
  8. Deary Ian J, Gow Alan J, Taylor Michelle D, Corley Janie, Brett Caroline, Wilson Valerie, Campbell Harry, Whalley Lawrence J, Visscher Peter M, Porteous David J, Starr John M, The Lothian Birth Cohort 1936: a study to examine influences on cognitive ageing from age 11 to age 70 and beyond, 10.1186/1471-2318-7-28
  9. Deary I. J., Gow A. J., Pattie A., Starr J. M., Cohort Profile: The Lothian Birth Cohorts of 1921 and 1936, 10.1093/ije/dyr197
  10. Devuyst O., Pirson Y., Genetics of hypercalciuric stone forming diseases, 10.1038/sj.ki.5002441
  11. Devuyst Olivier, Knoers Nine V A M, Remuzzi Giuseppe, Schaefer Franz, Rare inherited kidney diseases: challenges, opportunities, and perspectives, 10.1016/s0140-6736(14)60659-0
  12. Dimke H., Desai P., Borovac J., Lau A., Pan W., Alexander R. T., Activation of the Ca2+-sensing receptor increases renal claudin-14 expression and urinary Ca2+ excretion, 10.1152/ajprenal.00263.2012
  13. Elkouby-Naor Liron, Abassi Zaid, Lagziel Ayala, Gow Alexander, Ben-Yosef Tamar, Double gene deletion reveals lack of cooperation between claudin 11 and claudin 14 tight junction proteins, 10.1007/s00441-008-0621-9
  14. Firmann Mathieu, Mayor Vladimir, Vidal Pedro Marques, Bochud Murielle, Pécoud Alain, Hayoz Daniel, Paccaud Fred, Preisig Martin, Song Kijoung S, Yuan Xin, Danoff Theodore M, Stirnadel Heide A, Waterworth Dawn, Mooser Vincent, Waeber Gérard, Vollenweider Peter, The CoLaus study: a population-based study to investigate the epidemiology and genetic determinants of cardiovascular risk factors and metabolic syndrome, 10.1186/1471-2261-8-6
  15. Glaudemans Bob, Terryn Sara, Gölz Nadine, Brunati Martina, Cattaneo Angela, Bachi Angela, Al-Qusairi Lama, Ziegler Urs, Staub Olivier, Rampoldi Luca, Devuyst Olivier, A primary culture system of mouse thick ascending limb cells with preserved function and uromodulin processing, 10.1007/s00424-013-1321-1
  16. Gong Yongfeng, Renigunta Vijayaram, Himmerkus Nina, Zhang Jiaqi, Renigunta Aparna, Bleich Markus, Hou Jianghui, Claudin-14 regulates renal Ca++transport in response to CaSR signalling via a novel microRNA pathway : Claudin-14 function and regulation, 10.1038/emboj.2012.49
  17. Groenestege W. M. T., The Epithelial Mg2+ Channel Transient Receptor Potential Melastatin 6 Is Regulated by Dietary Mg2+ Content and Estrogens, 10.1681/asn.2005070700
  18. Himmerkus N., Shan Q., Goerke B., Hou J., Goodenough D. A., Bleich M., Salt and acid-base metabolism in claudin-16 knockdown mice: impact for the pathophysiology of FHHNC patients, 10.1152/ajprenal.90388.2008
  19. Hou J., Paracellin-1 and the modulation of ion selectivity of tight junctions, 10.1242/jcs.02631
  20. Hou Jianghui, Shan Qixian, Wang Tong, Gomes Antonio S., Yan QingShang, Paul David L., Bleich Markus, Goodenough Daniel A., Transgenic RNAi Depletion of Claudin-16 and the Renal Handling of Magnesium, 10.1074/jbc.m700632200
  21. Hou J, Renigunta A, Konrad M, Gomes A, Schneeberger E, Paul D, Goodenough DA (2008) Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex. J Clin Invest 118:619–628. doi: 10.1172/JCI33970DS1
  22. Hou J., Renigunta A., Gomes A. S., Hou M., Paul D. L., Waldegger S., Goodenough D. A., Claudin-16 and claudin-19 interaction is required for their assembly into tight junctions and for renal reabsorption of magnesium, 10.1073/pnas.0907724106
  23. Houillier Pascal, Mechanisms and Regulation of Renal Magnesium Transport, 10.1146/annurev-physiol-021113-170336
  24. Ikari Akira, Hirai Naho, Shiroma Morihiko, Harada Hitoshi, Sakai Hideki, Hayashi Hisayoshi, Suzuki Yuichi, Degawa Masakuni, Takagi Kuniaki, Association of Paracellin-1 with ZO-1 Augments the Reabsorption of Divalent Cations in Renal Epithelial Cells, 10.1074/jbc.m406331200
  25. Kausalya P. J., Disease-associated mutations affect intracellular traffic and paracellular Mg2+ transport function of Claudin-16, 10.1172/jci26323
  26. Konrad Martin, Schaller André, Seelow Dominik, Pandey Amit V., Waldegger Siegfried, Lesslauer Annegret, Vitzthum Helga, Suzuki Yoshiro, Luk John M., Becker Christian, Schlingmann Karl P., Schmid Marcel, Rodriguez-Soriano Juan, Ariceta Gema, Cano Francisco, Enriquez Ricardo, Jüppner Harald, Bakkaloglu Sevcan A., Hediger Matthias A., Gallati Sabina, Neuhauss Stephan C.F., Nürnberg Peter, Weber Stefanie, Mutations in the Tight-Junction Gene Claudin 19 (CLDN19) Are Associated with Renal Magnesium Wasting, Renal Failure, and Severe Ocular Involvement, 10.1086/508617
  27. Lalioti Maria D, Zhang Junhui, Volkman Heather M, Kahle Kristopher T, Hoffmann Kristin E, Toka Hakan R, Nelson-Williams Carol, Ellison David H, Flavell Richard, Booth Carmen J, Lu Yin, Geller David S, Lifton Richard P, Wnk4 controls blood pressure and potassium homeostasis via regulation of mass and activity of the distal convoluted tubule, 10.1038/ng1877
  28. Meyer Tamra E., Verwoert Germaine C., Hwang Shih-Jen, Glazer Nicole L., Smith Albert V., van Rooij Frank J. A., Ehret Georg B., Boerwinkle Eric, Felix Janine F., Leak Tennille S., Harris Tamara B., Yang Qiong, Dehghan Abbas, Aspelund Thor, Katz Ronit, Homuth Georg, Kocher Thomas, Rettig Rainer, Ried Janina S., Gieger Christian, Prucha Hanna, Pfeufer Arne, Meitinger Thomas, Coresh Josef, Hofman Albert, Sarnak Mark J., Chen Yii-Der Ida, Uitterlinden André G., Chakravarti Aravinda, Psaty Bruce M., van Duijn Cornelia M., Kao W. H. Linda, Witteman Jacqueline C. M., Gudnason Vilmundur, Siscovick David S., Fox Caroline S., Köttgen Anna, , , Genome-Wide Association Studies of Serum Magnesium, Potassium, and Sodium Concentrations Identify Six Loci Influencing Serum Magnesium Levels, 10.1371/journal.pgen.1001045
  29. Müller Dominik, Kausalya P. Jaya, Claverie-Martin Felix, Meij Iwan C., Eggert Paul, Garcia-Nieto Victor, Hunziker Walter, A Novel Claudin 16 Mutation Associated with Childhood Hypercalciuria Abolishes Binding to ZO-1 and Results in Lysosomal Mistargeting, 10.1086/380418
  30. Muto Shigeaki, Hata Masaki, Taniguchi Junichi, Tsuruoka Shuichi, Moriwaki Kazumasa, Saitou Mitinori, Furuse Kyoko, Sasaki Hiroyuki, Fujimura Akio, Imai Masashi, Kusano Eiji, Tsukita Shoichiro, Furuse Mikio, Claudin-2–deficient mice are defective in the leaky and cation-selective paracellular permeability properties of renal proximal tubules, 10.1073/pnas.0912901107
  31. O'Seaghdha Conall M., Wu Hongsheng, Yang Qiong, Kapur Karen, Guessous Idris, Zuber Annie Mercier, Köttgen Anna, Stoudmann Candice, Teumer Alexander, Kutalik Zoltán, Mangino Massimo, Dehghan Abbas, Zhang Weihua, Eiriksdottir Gudny, Li Guo, Tanaka Toshiko, Portas Laura, Lopez Lorna M., Hayward Caroline, Lohman Kurt, Matsuda Koichi, Padmanabhan Sandosh, Firsov Dmitri, Sorice Rossella, Ulivi Sheila, Brockhaus A. Catharina, Kleber Marcus E., Mahajan Anubha, Ernst Florian D., Gudnason Vilmundur, Launer Lenore J., Mace Aurelien, Boerwinckle Eric, Arking Dan E., Tanikawa Chizu, Nakamura Yusuke, Brown Morris J., Gaspoz Jean-Michel, Theler Jean-Marc, Siscovick David S., Psaty Bruce M., Bergmann Sven, Vollenweider Peter, Vitart Veronique, Wright Alan F., Zemunik Tatijana, Boban Mladen, Kolcic Ivana, Navarro Pau, Brown Edward M., Estrada Karol, Ding Jingzhong, Harris Tamara B., Bandinelli Stefania, Hernandez Dena, Singleton Andrew B., Girotto Giorgia, Ruggiero Daniela, d'Adamo Adamo Pio, Robino Antonietta, Meitinger Thomas, Meisinger Christa, Davies Gail, Starr John M., Chambers John C., Boehm Bernhard O., Winkelmann Bernhard R., Huang Jie, Murgia Federico, Wild Sarah H., Campbell Harry, Morris Andrew P., Franco Oscar H., Hofman Albert, Uitterlinden Andre G., Rivadeneira Fernando, Völker Uwe, Hannemann Anke, Biffar Reiner, Hoffmann Wolfgang, Shin So–Youn, Lescuyer Pierre, Henry Hughes, Schurmann Claudia, Munroe Patricia B., Gasparini Paolo, Pirastu Nicola, Ciullo Marina, Gieger Christian, März Winfried, Lind Lars, Spector Tim D., Smith Albert V., Rudan Igor, Wilson James F., Polasek Ozren, Deary Ian J., Pirastu Mario, Ferrucci Luigi, Liu Yongmei, Kestenbaum Bryan, Kooner Jaspal S., Witteman Jacqueline C. M., Nauck Matthias, Kao W. H. Linda, Wallaschofski Henri, Bonny Olivier, Fox Caroline S., Bochud Murielle, , , Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations, 10.1371/journal.pgen.1003796
  32. Polašek Ozren, Marušić Ana, Rotim Krešimir, Hayward Caroline, Vitart Veronique, Huffman Jennifer, Campbell Susan, Janković Stipan, Boban Mladen, Biloglav Zrinka, Kolčić Ivana, Krželj Vjekoslav, Terzić Janoš, Matec Lana, Tometić Gordan, Nonković Dijana, Ninčević Jasna, Pehlić Marina, Žedelj Jurica, Velagić Vedran, Juričić Danica, Kirac Iva, Belak Kovačević Sanja, Wright Alan F., Campbell Harry, Rudan Igor, Genome-wide Association Study of Anthropometric Traits in Korčula Island, Croatia, 10.3325/cmj.2009.50.7
  33. Praga Manuel, Vara Julia, González-Parra Emilio, Andrés Amado, Alamo Concepción, Araque Alicia, Ortiz Arturo, Rodicio José Luis, Familial hypomagnesemia with hypercalciuria and nephrocalcinosis, 10.1038/ki.1995.199
  34. Quamme Gary A., Renal magnesium handling: New insights in understanding old problems, 10.1038/ki.1997.443
  35. Rozen S, Skaletsky H (2000) Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132:365–386
  36. Rudan Igor, Marušić Ana, Janković Stipan, Rotim Krešimir, Boban Mladen, Lauc Gordan, Grković Ivica, Đogaš Zoran, Zemunik Tatijana, Vatavuk Zoran, Benčić Goran, Rudan Diana, Mulić Rosanda, Krželj Vjekoslav, Terzić Janoš, Stojanović Dražen, Puntarić Dinko, Bilić Ervina, Ropac Darko, Vorko-Jović Ariana, Znaor Ariana, Stevanović Ranko, Biloglav Zrinka, Polašek Ozren, “10 001 Dalmatians:” Croatia Launches Its National Biobank, 10.3325/cmj.2009.50.4
  37. Schweigel-Röntgen M (2014) The families of zinc (SLC30 and SLC39) and copper (SLC31) transporters. In: Curr. Top. Membr. In: Bevens. Elsevier, Amsterdam, pp. 321–355
  38. Simon D. B., Paracellin-1, a Renal Tight Junction Protein Required for Paracellular Mg2+ Resorption, 10.1126/science.285.5424.103
  39. Takahashi N., Chernavvsky D. R., Gomez R. A., Igarashi P., Gitelman H. J., Smithies O., Uncompensated polyuria in a mouse model of Bartter's syndrome, 10.1073/pnas.090091297
  40. Thorleifsson Gudmar, Holm Hilma, Edvardsson Vidar, Walters G Bragi, Styrkarsdottir Unnur, Gudbjartsson Daniel F, Sulem Patrick, Halldorsson Bjarni V, de Vegt Femmie, d'Ancona Frank C H, den Heijer Martin, Franzson Leifur, Christiansen Claus, Alexandersen Peter, Rafnar Thorunn, Kristjansson Kristleifur, Sigurdsson Gunnar, Kiemeney Lambertus A, Bodvarsson Magnus, Indridason Olafur S, Palsson Runolfur, Kong Augustine, Thorsteinsdottir Unnur, Stefansson Kari, Sequence variants in the CLDN14 gene associate with kidney stones and bone mineral density, 10.1038/ng.404
  41. Toka Hakan R., Genovese Giulio, Mount David B., Pollak Martin R., Curhan Gary C., Frequency of Rare Allelic Variation in Candidate Genes among Individuals with Low and High Urinary Calcium Excretion, 10.1371/journal.pone.0071885
  42. Traglia Michela, Sala Cinzia, Masciullo Corrado, Cverhova Valeria, Lori Francesca, Pistis Giorgio, Bione Silvia, Gasparini Paolo, Ulivi Sheila, Ciullo Marina, Nutile Teresa, Bosi Emanuele, Sirtori Marcella, Mignogna Giovanna, Rubinacci Alessandro, Buetti Iwan, Camaschella Clara, Petretto Enrico, Toniolo Daniela, Heritability and Demographic Analyses in the Large Isolated Population of Val Borbera Suggest Advantages in Mapping Complex Traits Genes, 10.1371/journal.pone.0007554
  43. Tuschl K, Clayton PT, Gospe SM, Mills PB (2012) Dystonia/parkinsonism, hypermanganesemia, polycythemia, and chronic liver disease. In: Pragon RA et al. (ed) GeneReviews [Internet] Seattle (WA): University of Washington, Seattle; 1993–2016
  44. van Angelen A. A., San-Cristobal P., Pulskens W. P., Hoenderop J. G., Bindels R. J., The impact of dietary magnesium restriction on magnesiotropic and calciotropic genes, 10.1093/ndt/gft358
  45. Vitart Veronique, Rudan Igor, Hayward Caroline, Gray Nicola K, Floyd James, Palmer Colin NA, Knott Sara A, Kolcic Ivana, Polasek Ozren, Graessler Juergen, Wilson James F, Marinaki Anthony, Riches Philip L, Shu Xinhua, Janicijevic Branka, Smolej-Narancic Nina, Gorgoni Barbara, Morgan Joanne, Campbell Susan, Biloglav Zrinka, Barac-Lauc Lovorka, Pericic Marijana, Klaric Irena Martinovic, Zgaga Lina, Skaric-Juric Tatjana, Wild Sarah H, Richardson William A, Hohenstein Peter, Kimber Charley H, Tenesa Albert, Donnelly Louise A, Fairbanks Lynette D, Aringer Martin, McKeigue Paul M, Ralston Stuart H, Morris Andrew D, Rudan Pavao, Hastie Nicholas D, Campbell Harry, Wright Alan F, SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout, 10.1038/ng.106
  46. Wilcox Edward R, Burton Quianna L, Naz Sadaf, Riazuddin Saima, Smith Tenesha N, Ploplis Barbara, Belyantseva Inna, Ben-Yosef Tamar, Liburd Nikki A, Morell Robert J, Kachar Bechara, Wu Doris K, Griffith Andrew J, Riazuddin Sheikh, Friedman Thomas B, Mutations in the Gene Encoding Tight Junction Claudin-14 Cause Autosomal Recessive Deafness DFNB29, 10.1016/s0092-8674(01)00200-8
  47. Will C., Breiderhoff T., Thumfart J., Stuiver M., Kopplin K., Sommer K., Gunzel D., Querfeld U., Meij I. C., Shan Q., Bleich M., Willnow T. E., Muller D., Targeted deletion of murine Cldn16 identifies extra- and intrarenal compensatory mechanisms of Ca2+ and Mg2+ wasting, 10.1152/ajprenal.00499.2009
  48. Yu A. S. L., Claudins and the Kidney, 10.1681/asn.2014030284
Bibliographic reference Corre, Tanguy ; Olinger, Eric ; Harris, Sarah E ; Traglia, Michela ; Ulivi, Sheila ; et. al. Common variants in CLDN14 are associated with differential excretion of magnesium over calcium in urine.. In: Pflügers Archiv - European journal of physiology, Vol. 469, no. 1, p. 91-103 (2017)
Permanent URL http://hdl.handle.net/2078.1/179184