Teumer, Alexander and Tin, Adrienne and Sorice, Rossella and Gorski, Mathias and Yeo, Nan Cher and Chu, Audrey Y. and Li, Man and Li, Yong and Mijatovic, Vladan and Ko, Yi-An and Taliun, Daniel and Luciani, Alessandro and Chen, Ming-Huei and Yang, Qiong and Foster, Meredith C. and Olden, Matthias and Hiraki, Linda T. and Tayo, Bamidele O. and Fuchsberger, Christian and Dieffenbach, Aida Karina and Shuldiner, Alan R. and Smith, Albert V. and Zappa, Allison M. and Lupo, Antonio and Kollerits, Barbara and Ponte, Belen and Stengel, Benedicte and Kraemer, Bernhard K. and Paulweber, Bernhard and Mitchell, Braxton D. and Hayward, Caroline and Helmer, Catherine and Meisinger, Christa and Gieger, Christian and Shaffer, Christian M. and Mueller, Christian and Langenberg, Claudia and Ackermann, Daniel and Siscovick, David and Boerwinkle, Eric and Kronenberg, Florian and Ehret, Georg B. and Homuth, Georg and Waeber, Gerard and Navis, Gerjan and Gambaro, Giovanni and Malerba, Giovanni and Eiriksdottir, Gudny and Li, Guo and Wichmann, H. Erich and Grallert, Harald and Wallaschofski, Henri and Voelzke, Henry and Brenner, Herrmann and Kramer, Holly and Leach, I. Mateo and Rudan, Igor and Hillege, Hans L. and Beckmann, Jacques S. and Lambert, Jean Charles and Luan, Jian'an and Zhao, Jing Hua and Chalmers, John and Coresh, Josef and Denny, Joshua C. and Butterbach, Katja and Launer, Lenore J. and Ferrucci, Luigi and Kedenko, Lyudmyla and Haun, Margot and Metzger, Marie and Woodward, Mark and Hoffman, Matthew J. and Nauck, Matthias and Waldenberger, Melanie and Pruijm, Menno and Bochud, Murielle and Rheinberger, Myriam and Verweij, Niek and Wareham, Nicholas J. and Endlich, Nicole and Soranzo, Nicole and Polasek, Ozren and van der Harst, Pim and Pramstaller, Peter Paul and Vollenweider, Peter and Wild, Philipp S. and Gansevoort, Ron T. and Rettig, Rainer and Biffar, Reiner and Carroll, Robert J. and Katz, Ronit and Loos, Ruth J. F. and Hwang, Shih-Jen and Coassin, Stefan and Bergmann, Sven and Rosas, Sylvia E. and Stracke, Sylvia and Harris, Tamara B. and Corre, Tanguy and Zeller, Tanja and Illig, Thomas and Aspelund, Thor and Tanaka, Toshiko and Lendeckel, Uwe and Volker, Uwe and Gudnason, Vilmundur and Chouraki, Vincent and Koenig, Wolfgang and Kutalik, Zoltan and O'Connell, Jeffrey R. and Parsa, Afshin and Heid, Iris M. and Paterson, Andrew D. and de Boer, Ian H. and Devuyst, Olivier and Lazar, Jozef and Endlich, Karlhans and Susztak, Katalin and Tremblay, Johanne and Hamet, Pavel and Jacob, Howard J. and Boeger, Carsten A. and Fox, Caroline S. and Pattaro, Cristian and Koettgen, Anna (2016) Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes. DIABETES, 65 (3). pp. 803-817. ISSN 0012-1797, 1939-327X
Full text not available from this repository.Abstract
Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 x 10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 x 10(-7)) and 13% for RAB38/CTSC (P = 5.8 x 10(-7)). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLOMERULAR-FILTRATION-RATE; RISK POPULATION COHORTS; KIDNEY-DISEASE; COLLABORATIVE METAANALYSIS; MODULATES PROTEINURIA; EXPRESSION; HERITABILITY; MORTALITY; INSIGHTS; RAB38; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie Medicine > Institut für Epidemiologie und Präventivmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Mar 2019 10:37 |
| Last Modified: | 12 Mar 2019 10:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2350 |
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