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Genome-Wide Meta-Analysis Unravels Interactions between Magnesium Homeostasis and Metabolic Phenotypes.
Corre, Tanguy; Arjona, Francisco J; Hayward, Caroline; Youhanna, Sonia; de Baaij, Jeroen H F; Belge, Hendrica; Nägele, Nadine; Debaix, Huguette; Blanchard, Maxime G; Traglia, Michela; Harris, Sarah E; Ulivi, Sheila; Rueedi, Rico; Lamparter, David; Macé, Aurélien; Sala, Cinzia; Lenarduzzi, Stefania; Ponte, Belen; Pruijm, Menno; Ackermann, Daniel; Ehret, Georg; Baptista, Daniela; Polasek, Ozren; Rudan, Igor; Hurd, Toby W; Hastie, Nicholas D; Vitart, Veronique; Waeber, Geràrd; Kutalik, Zoltán; Bergmann, Sven; Vargas-Poussou, Rosa; Konrad, Martin; Gasparini, Paolo; Deary, Ian J; Starr, John M; Toniolo, Daniela; Vollenweider, Peter; Hoenderop, Joost G J; Bindels, René J M; Bochud, Murielle; Devuyst, Olivier.
Afiliação
  • Corre T; Institute of Social and Preventive Medicine.
  • Arjona FJ; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
  • Hayward C; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Youhanna S; Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
  • de Baaij JHF; Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine.
  • Belge H; Institute of Physiology, University of Zürich, Zurich, Switzerland.
  • Nägele N; Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Debaix H; Institute of Physiology, University of Zürich, Zurich, Switzerland.
  • Blanchard MG; Institute of Physiology, University of Zürich, Zurich, Switzerland.
  • Traglia M; Institute of Physiology, University of Zürich, Zurich, Switzerland.
  • Harris SE; Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Ulivi S; Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
  • Rueedi R; Centre for Cognitive Ageing and Cognitive Epidemiology.
  • Lamparter D; Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and Medical Research Council Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, UK.
  • Macé A; Department of Medical Genetics, Institute for Maternal and Child Health, Istituto di Ricovero e Cura a Carattere Scientifico "Burlo Garofolo," Trieste, Italy.
  • Sala C; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
  • Lenarduzzi S; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Ponte B; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
  • Pruijm M; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Ackermann D; Institute of Social and Preventive Medicine.
  • Ehret G; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Baptista D; Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
  • Polasek O; Department of Medical Genetics, Institute for Maternal and Child Health, Istituto di Ricovero e Cura a Carattere Scientifico "Burlo Garofolo," Trieste, Italy.
  • Rudan I; Service of Nephrology and.
  • Hurd TW; Service of Nephrology, University Hospital of Lausanne, Lausanne, Switzerland.
  • Hastie ND; University Clinic for Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Vitart V; Division of Cardiology, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland.
  • Waeber G; Division of Cardiology, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland.
  • Kutalik Z; Faculty of Medicine, University of Split, Split, Croatia.
  • Bergmann S; Usher Institute of Population Health Sciences and Informatics.
  • Vargas-Poussou R; Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine.
  • Konrad M; Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine.
  • Gasparini P; Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine.
  • Deary IJ; Department of Medicine, Internal Medicine, and.
  • Starr JM; Institute of Social and Preventive Medicine.
  • Toniolo D; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Vollenweider P; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
  • Hoenderop JGJ; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Bindels RJM; Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa.
  • Bochud M; Department of Genetics, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, Paris, France.
  • Devuyst O; Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte, Paris, France.
J Am Soc Nephrol ; 29(1): 335-348, 2018 01.
Article em En | MEDLINE | ID: mdl-29093028
Magnesium (Mg2+) homeostasis is critical for metabolism. However, the genetic determinants of the renal handling of Mg2+, which is crucial for Mg2+ homeostasis, and the potential influence on metabolic traits in the general population are unknown. We obtained plasma and urine parameters from 9099 individuals from seven cohorts, and conducted a genome-wide meta-analysis of Mg2+ homeostasis. We identified two loci associated with urinary magnesium (uMg), rs3824347 (P=4.4×10-13) near TRPM6, which encodes an epithelial Mg2+ channel, and rs35929 (P=2.1×10-11), a variant of ARL15, which encodes a GTP-binding protein. Together, these loci account for 2.3% of the variation in 24-hour uMg excretion. In human kidney cells, ARL15 regulated TRPM6-mediated currents. In zebrafish, dietary Mg2+ regulated the expression of the highly conserved ARL15 ortholog arl15b, and arl15b knockdown resulted in renal Mg2+ wasting and metabolic disturbances. Finally, ARL15 rs35929 modified the association of uMg with fasting insulin and fat mass in a general population. In conclusion, this combined observational and experimental approach uncovered a gene-environment interaction linking Mg2+ deficiency to insulin resistance and obesity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Ribosilação do ADP / Canais de Cátion TRPM / Homeostase / Rim / Magnésio Tipo de estudo: Prognostic_studies / Systematic_reviews Limite: Animals / Humans Idioma: En Revista: J Am Soc Nephrol Assunto da revista: NEFROLOGIA Ano de publicação: 2018 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Ribosilação do ADP / Canais de Cátion TRPM / Homeostase / Rim / Magnésio Tipo de estudo: Prognostic_studies / Systematic_reviews Limite: Animals / Humans Idioma: En Revista: J Am Soc Nephrol Assunto da revista: NEFROLOGIA Ano de publicação: 2018 Tipo de documento: Article