CUBN Is a Gene Locus for Albuminuria

Carsten A. Böger; Ming-Huei Chen; Adrienne Tin; Matthias Olden; Anna Köttgen; Ian H. de Boer; Christian Fuchsberger; Conall M. O'Seaghdha; Cristian Pattaro; Alexander Teumer; Ching-Ti Liu; Nicole L. Glazer; Man Li; Jeffrey R. O'Connell; Toshiko Tanaka; Carmen A. Peralta; Zoltán Kutalik; Jian'an Luan; Jing Hua Zhao; Shih-Jen Hwang; Ermeg Akylbekova; Holly Kramer; Pim van der Harst; Albert V. Smith; Kurt Lohman; Mariza de Andrade; Caroline Hayward; Barbara Kollerits; Anke Tönjes; Thor Aspelund; Erik Ingelsson; Gudny Eiriksdottir; Lenore J. Launer; Tamara B. Harris; Alan R. Shuldiner; Braxton D. Mitchell; Dan E. Arking; Nora Franceschini; Eric Boerwinkle; Josephine Egan; Dena Hernandez; Muredach Reilly; Raymond R. Townsend; Thomas Lumley; David S. Siscovick; Bruce M. Psaty; Bryan Kestenbaum; Talin Haritunians; Sven Bergmann; Peter Vollenweider; Gerard Waeber; Vincent Mooser; Dawn Waterworth; Andrew D. Johnson; Jose C. Florez; James B. Meigs; Xiaoning Lu; Stephen T. Turner; Elizabeth J. Atkinson; Tennille S. Leak; Knut Aasarød; Frank Skorpen; Ann-Christine Syvänen; Thomas Illig; Jens Baumert; Wolfgang Koenig; Bernhard K. Krämer; Olivier Devuyst; Josyf C. Mychaleckyj; Cosetta Minelli; Stephan J.L. Bakker; Lyudmyla Kedenko; Bernhard Paulweber; Stefan Coassin; Karlhans Endlich; Heyo K. Kroemer; Reiner Biffar; Sylvia Stracke; Henry Völzke; Michael Stumvoll; Reedik Mägi; Harry Campbell; Veronique Vitart; Nicholas D. Hastie; Vilmundur Gudnason; Sharon L.R. Kardia; Yongmei Liu; Ozren Polasek; Gary Curhan; Florian Kronenberg; Inga Prokopenko; Igor Rudan; Johan Ärnlöv; Stein Hallan; Gerjan Navis; Afshin Parsa; Luigi Ferrucci; Josef Coresh; DCCT EDIC; Michael G. Shlipak

doi:10.1681/ASN.2010060598

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CUBN Is a Gene Locus for Albuminuria

Carsten A. Böger, Ming-Huei Chen, Adrienne Tin, Matthias Olden, Anna Köttgen, Ian H. de Boer, Christian Fuchsberger, Conall M. O'Seaghdha, Cristian Pattaro, Alexander Teumer, …

Journal of the American Society of Nephrology, Vol.22(3), pp.555-570

01/03/2011

DOI: https://doi.org/10.1681/ASN.2010060598

PMID: 21355061

Abstract

Clinical Research

Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR ( P = 1.1 × 10 −11 ) and microalbuminuria ( P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.

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Title: CUBN Is a Gene Locus for Albuminuria
Creators: Carsten A. Böger - Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany
Ming-Huei Chen - Boston University School of Medicine
Adrienne Tin - Johns Hopkins University
Matthias Olden
Anna Köttgen
Ian H. de Boer - University of Washington
Christian Fuchsberger - University of Lübeck
Conall M. O'Seaghdha - Brigham and Women's Hospital
Cristian Pattaro - University of Lübeck
Alexander Teumer - Universität Greifswald
Ching-Ti Liu - Boston University
Nicole L. Glazer - University of Washington
Man Li - Johns Hopkins University
Jeffrey R. O'Connell - University of Maryland School of Medicine, Baltimore, Maryland
Toshiko Tanaka
Carmen A. Peralta - University of California, San Francisco
Zoltán Kutalik
Jian'an Luan - MRC Epidemiology Unit
Jing Hua Zhao - MRC Epidemiology Unit
Shih-Jen Hwang - Framingham Heart Study
Ermeg Akylbekova - Jackson State University
Holly Kramer - Universidad Loyola Andalucía
Pim van der Harst - University Medical Center Groningen
Albert V. Smith
Kurt Lohman - Wake Forest University
Mariza de Andrade - Mayo Clinic
Caroline Hayward - MRC Human Genetics Unit
Barbara Kollerits - Innsbruck Medical University
Anke Tönjes - Department of Medicine, University of Leipzig, Leipzig, Germany
Thor Aspelund
Erik Ingelsson - Karolinska Institutet
Gudny Eiriksdottir - Icelandic Heart Association
Lenore J. Launer - Laboratory of Epidemiology, Demography, and Biometry, NIA, Bethesda, Maryland
Tamara B. Harris - Laboratory of Epidemiology, Demography, and Biometry, NIA, Bethesda, Maryland
Alan R. Shuldiner - University of Maryland School of Medicine, Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland
Braxton D. Mitchell - University of Maryland School of Medicine, Baltimore, Maryland
Dan E. Arking - McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland
Nora Franceschini - University of North Carolina at Chapel Hill
Eric Boerwinkle - Human Genetics Center, University of Texas Health Science Center, Houston, Texas
Josephine Egan - National Institute on Aging
Dena Hernandez - National Institute on Aging
Muredach Reilly - University of Pennsylvania
Raymond R. Townsend - University of Pennsylvania
Thomas Lumley - University of Washington
David S. Siscovick - University of Washington
Bruce M. Psaty - Group Health Cooperative
Bryan Kestenbaum - University of Washington
Talin Haritunians - Cedars-Sinai Medical Center
Sven Bergmann
Peter Vollenweider - Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Gerard Waeber - Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Vincent Mooser - GlaxoSmithKline
Dawn Waterworth - GlaxoSmithKline
Andrew D. Johnson - Framingham Heart Study
Jose C. Florez - Harvard Medical School
James B. Meigs - Department of General Internal Medicine, Massachussetts General Hospital, Boston, Massachusetts
Xiaoning Lu - Boston University
Stephen T. Turner - Mayo Clinic
Elizabeth J. Atkinson - Mayo Clinic
Tennille S. Leak - University of Pittsburgh
Knut Aasarød
Frank Skorpen - Norwegian University of Science and Technology
Ann-Christine Syvänen - Uppsala University
Thomas Illig - Helmholtz Zentrum München
Jens Baumert - Helmholtz Zentrum München
Wolfgang Koenig - Zentrum für Innere Medizin, Klinik für Innere Medizin II - Kardiologie, Universitätsklinikum Ulm, Ulm, Germany
Bernhard K. Krämer - University Medical Centre Mannheim
Olivier Devuyst - UCLouvain
Josyf C. Mychaleckyj - Genomics
Cosetta Minelli - University of Lübeck
Stephan J.L. Bakker - University Medical Center Groningen
Lyudmyla Kedenko - Paracelsus Medical University
Bernhard Paulweber - Paracelsus Medical University
Stefan Coassin - Innsbruck Medical University
Karlhans Endlich - Universität Greifswald
Heyo K. Kroemer - Universität Greifswald
Reiner Biffar - Universität Greifswald
Sylvia Stracke - Universität Greifswald
Henry Völzke - Universität Greifswald
Michael Stumvoll - Department of Medicine, University of Leipzig, Leipzig, Germany
Reedik Mägi - University of Oxford
Harry Campbell - University of Edinburgh
Veronique Vitart - MRC Human Genetics Unit
Nicholas D. Hastie - MRC Human Genetics Unit
Vilmundur Gudnason
Sharon L.R. Kardia - University of Michigan–Ann Arbor
Yongmei Liu - Wake Forest University
Ozren Polasek - Gen-info
Gary Curhan - Brigham and Women's Hospital
Florian Kronenberg - Innsbruck Medical University
Inga Prokopenko - University of Oxford
Igor Rudan - University of Edinburgh
Johan Ärnlöv - Uppsala University
Stein Hallan
Gerjan Navis - University Medical Center Groningen
Afshin Parsa - University of Maryland School of Medicine, Baltimore, Maryland
Luigi Ferrucci - National Institute on Aging
Josef Coresh - Johns Hopkins University
DCCT EDIC
Michael G. Shlipak - University of California, San Francisco
Publication Details: Journal of the American Society of Nephrology, Vol.22(3), pp.555-570
Publisher: American Society of Nephrology
Number of pages: 16
Date published: 01/03/2011
Identifiers: 99928668302346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

CUBN Is a Gene Locus for Albuminuria

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