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CUBN is a gene locus for albuminuria.


ABSTRACT: 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.

SUBMITTER: Boger CA 

PROVIDER: S-EPMC3060449 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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CUBN is a gene locus for albuminuria.

Böger Carsten A CA   Chen Ming-Huei MH   Tin Adrienne A   Olden Matthias M   Köttgen Anna A   de Boer Ian H IH   Fuchsberger Christian C   O'Seaghdha Conall M CM   Pattaro Cristian C   Teumer Alexander A   Liu Ching-Ti CT   Glazer Nicole L NL   Li Man M   O'Connell Jeffrey R JR   Tanaka Toshiko T   Peralta Carmen A CA   Kutalik Zoltán Z   Luan Jian'an J   Zhao Jing Hua JH   Hwang Shih-Jen SJ   Akylbekova Ermeg E   Kramer Holly H   van der Harst Pim P   Smith Albert V AV   Lohman Kurt K   de Andrade Mariza M   Hayward Caroline C   Kollerits Barbara B   Tönjes Anke A   Aspelund Thor T   Ingelsson Erik E   Eiriksdottir Gudny G   Launer Lenore J LJ   Harris Tamara B TB   Shuldiner Alan R AR   Mitchell Braxton D BD   Arking Dan E DE   Franceschini Nora N   Boerwinkle Eric E   Egan Josephine J   Hernandez Dena D   Reilly Muredach M   Townsend Raymond R RR   Lumley Thomas T   Siscovick David S DS   Psaty Bruce M BM   Kestenbaum Bryan B   Haritunians Talin T   Bergmann Sven S   Vollenweider Peter P   Waeber Gerard G   Mooser Vincent V   Waterworth Dawn D   Johnson Andrew D AD   Florez Jose C JC   Meigs James B JB   Lu Xiaoning X   Turner Stephen T ST   Atkinson Elizabeth J EJ   Leak Tennille S TS   Aasarød Knut K   Skorpen Frank F   Syvänen Ann-Christine AC   Illig Thomas T   Baumert Jens J   Koenig Wolfgang W   Krämer Bernhard K BK   Devuyst Olivier O   Mychaleckyj Josyf C JC   Minelli Cosetta C   Bakker Stephan J L SJ   Kedenko Lyudmyla L   Paulweber Bernhard B   Coassin Stefan S   Endlich Karlhans K   Kroemer Heyo K HK   Biffar Reiner R   Stracke Sylvia S   Völzke Henry H   Stumvoll Michael M   Mägi Reedik R   Campbell Harry H   Vitart Veronique V   Hastie Nicholas D ND   Gudnason Vilmundur V   Kardia Sharon L R SL   Liu Yongmei Y   Polasek Ozren O   Curhan Gary G   Kronenberg Florian F   Prokopenko Inga I   Rudan Igor I   Arnlöv Johan J   Hallan Stein S   Navis Gerjan G   Parsa Afshin A   Ferrucci Luigi L   Coresh Josef J   Shlipak Michael G MG   Bull Shelley B SB   Paterson Nicholas J NJ   Wichmann H-Erich HE   Wareham Nicholas J NJ   Loos Ruth J F RJ   Rotter Jerome I JI   Pramstaller Peter P PP   Cupples L Adrienne LA   Beckmann Jacques S JS   Yang Qiong Q   Heid Iris M IM   Rettig Rainer R   Dreisbach Albert W AW   Bochud Murielle M   Fox Caroline S CS   Kao W H L WH  

Journal of the American Society of Nephrology : JASN 20110301 3


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)  ...[more]

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