CUBN Is a Gene Locus for Albuminuria

被引：183

作者：

Boeger, Carsten A. ^{[2
]}

Chen, Ming-Huei ^{[3
]}

Tin, Adrienne ^{[4
,5
]}

Olden, Matthias ^{[2
,6
]}

Koettgen, Anna ^{[4
,5
,7
]}

de Boer, Ian H. ^{[8
]}

Fuchsberger, Christian ^{[9
,10
]}

O'Seaghdha, Conall M. ^{[11
,12
]}

Pattaro, Cristian ^{[9
,10
]}

Teumer, Alexander ^{[13
]}

Liu, Ching-Ti ^{[14
,15
]}

Glazer, Nicole L. ^{[16
,17
]}

Li, Man ^{[4
,5
]}

O'Conne, Jeffrey R. ^{[18
]}

Tanaka, Toshiko ^{[19
,20
]}

Peralta, Carmen A. ^{[21
,22
]}

Kutalik, Zoltan ^{[23
,24
]}

Luan, Jian'an ^{[25
]}

Zhao, Jing Hua ^{[25
]}

Hwang, Shih-Jen ^{[1
,27
]}

Akylbekova, Ermeg ^{[26
]}

Kramer, Holly ^{[28
]}

van der Harst, Pim ^{[29
]}

Smith, Albert V. ^{[30
,31
]}

Lohman, Kurt ^{[32
]}

de Andrade, Mariza ^{[33
]}

Hayward, Caroline ^{[34
]}

Kollerits, Barbara ^{[35
]}

Toenjes, Anke ^{[36
]}

Aspelund, Thor ^{[30
,31
]}

Ingelsson, Erik ^{[37
]}

Eiriksdottir, Gudny ^{[31
]}

Launer, Lenore J. ^{[38
]}

Harris, Tamara B. ^{[38
]}

Shuldiner, Alan R. ^{[39
]}

Mitchell, Braxton D.

Arking, Dan E. ^{[40
]}

Franceschini, Nora ^{[41
]}

Boerwinkle, Eric ^{[42
]}

Egan, Josephine ^{[43
]}

Hernandez, Dena ^{[44
]}

Reilly, Muredach ^{[45
]}

Townsend, Raymond R. ^{[46
]}

Lumley, Thomas ^{[16
,17
]}

Siscovick, David S. ^{[47
,48
]}

Psaty, Bruce M. ^{[49
,50
,51
,52
]}

Kestenbaum, Bryan ^{[8
]}

Haritunians, Talin ^{[53
]}

Bergmann, Sven ^{[23
,24
]}

Vollenweider, Peter ^{[54
]}

机构：

[1] NHLBIs Framingham Heart Study, Framingham, MA 01702 USA

[2] Univ Med Ctr Regensburg, Dept Internal Med 2, Regensburg, Germany

[3] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA

[4] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA

[5] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA

[6] Univ Regensburg, Dept Epidemiol & Prevent Med, Med Ctr, Regensburg, Germany

[7] Univ Hosp Freiburg, Div Renal, Freiburg, Germany

[8] Univ Washington, Div Nephrol, Seattle, WA 98195 USA

[9] European Acad Bolzano Bozen EURAC, Inst Med Genet, Bolzano, Italy

[10] Med Univ Lubeck, Affiliated Inst, D-23538 Lubeck, Germany

[11] Harvard Univ, Sch Med, Boston, MA USA

[12] Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA

[13] Ernst Moritz Arndt Univ Greifswald, Interfaculty Inst Genet & Funct Genom, Greifswald, Germany

[14] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[15] NHLBIs Framingham Heart Study, Boston, MA USA

[16] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[17] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[18] Univ Maryland, Sch Med, Baltimore, MD 21201 USA

[19] Medstar Res Inst, Baltimore, MD USA

[20] NIA, Clin Res Branch, Baltimore, MD 21224 USA

[21] Univ Calif San Francisco, Div Nephrol, San Francisco Med Sch, San Francisco, CA 94143 USA

[22] San Francisco VA Med Ctr, San Francisco, CA USA

[23] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland

[24] Swiss Inst Bioinformat, Lausanne, Switzerland

[25] Addenbrookes Hosp, MRC Epidemiol Unit, Inst Metab Sci, Cambridge, England

[26] Jackson State Univ, Jackson, MS USA

[27] Ctr Populat Studies, Framingham, MA USA

[28] Loyola Univ, Maywood, IL USA

[29] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands

[30] Univ Iceland, Reykjavik, Iceland

[31] Iceland Heart Assoc, Holtasmara, Kopavogur, Iceland

[32] Wake Forest Univ, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC 27109 USA

[33] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA

[34] Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland

[35] Innsbruck Med Univ, Div Genet Epidemiol, Innsbruck, Austria

[36] Univ Leipzig, Dept Med, Leipzig, Germany

[37] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[38] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA

[39] Univ Maryland, Sch Med, Geriatr Res & Educ Clin Ctr, Vet Adm Med Ctr, Baltimore, MD 21201 USA

[40] Johns Hopkins Med Inst, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA

[41] Univ N Carolina, Chapel Hill, NC USA

[42] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA

[43] NIA, Lab Clin Invest, Baltimore, MD 21224 USA

[44] NIA, Neurogenet Lab, Bethesda, MD 20892 USA

[45] Univ Penn, Div Cardiol, Perelman Ctr Adv Med, Philadelphia, PA 19104 USA

[46] Univ Penn, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA

[47] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[48] Univ Washington, Dept Med, Seattle, WA 98195 USA

[49] Grp Hlth Cooperat Puget Sound, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA USA

[50] Grp Hlth Cooperat Puget Sound, Dept Epidemiol, Seattle, WA USA

来源：

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2011年 / 22卷 / 03期

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; LOW-GRADE ALBUMINURIA; RENAL-FUNCTION; LINKAGE ANALYSIS; KIDNEY-FUNCTION; HEART; DISEASE; DESIGN; MICROALBUMINURIA; PROTEIN;

D O I：

10.1681/ASN.2010060598

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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 x 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.

引用

页码：555 / 570

页数：16

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