CUBN Is a Gene Locus for Albuminuria
Authors: 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, Michael G. Shlipak, Shelley B. Bull, Andrew D. Paterson, H.-Erich Wichmann, Nicholas J. Wareham, Ruth J.F. Loos, Jerome I. Rotter, Peter P. Pramstaller, L. Adrienne Cupples, Jacques S. Beckmann, Qiong Yang, Iris M. Heid, Rainer Rettig, Albert W. Dreisbach, Murielle Bochud, Caroline S. Fox, W.H.L. Kao
Journal: Journal of the American Society of Nephrology (2011)

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 <i>CUBN</i> gene, which encodes cubilin, and both UACR (<i>P</i> = 1.1 × 10<sup>−11</sup>) and microalbuminuria (<i>P</i> = 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 <i>CUBN</i> variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.