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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: ASN.2009070725v1 21/2/337    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Köttgen, A. Articles by Fox, C. S. PubMed PubMed Citation Articles by Köttgen, A. Articles by Fox, C. S. Related Collections Related Articles

Uromodulin Levels Associate with a Common UMOD Variant and Risk for Incident CKD

Anna Köttgen^*, Shih-Jen Hwang^,, Martin G. Larson, Jennifer E. Van Eyk^||, Qin Fu^||, Emelia J. Benjamin^,¶, Abbas Dehghan^**, Nicole L. Glazer, W.H. Linda Kao^*, Tamara B. Harris, Vilmundur Gudnason^,||||, Michael G. Shlipak^¶¶, Qiong Yang, Josef Coresh^*, Daniel Levy^, and Caroline S. Fox^,,***

*Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;
Framingham Heart Study, Framingham, Massachusetts;
Center for Population Studies, National Heart, Lung, and Blood Institute, and
Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, Maryland;
Departments of Biostatistics and
^¶Epidemiology, Boston University School of Public Health, Boston, Massachusetts;
^||Department of Medicine, Johns Hopkins University, Baltimore, Maryland;
**Department of Epidemiology, Erasmus Medical Centre, Rotterdam, Netherlands;
Cardiovascular Health Research Unit and Department of Medicine, University of Washington, Seattle, Washington;
Icelandic Heart Association Research Institute, Kopavogur, Iceland;
^||||University of Iceland, Reykjavik, Iceland;
^¶¶General Internal Medicine Division, San Francisco VA Medical Center, University of California, San Francisco, California; and
***Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

Correspondence: Dr. Caroline S. Fox, 73 Mount Wayte Avenue, Suite #2, Framingham, MA 01702. Phone: 508-935-3447; Fax: 508-626-1262; E-mail: foxca{at}nhlbi.nih.gov

Received for publication July 15, 2009. Accepted for publication October 13, 2009.

Common variants in the region of the UMOD gene, which encodes uromodulin (Tamm-Horsfall protein), associate with chronic kidney disease (CKD) and estimated GFR (eGFR). Whether uromodulin levels associate with UMOD variants or with the risk for developing CKD is unknown. We conducted an age- and gender-matched case-control study (n = 200) of incident CKD (eGFR <60 ml/min per 1.73 m²) within the Framingham Heart Study (FHS). Baseline urinary uromodulin concentrations were related to case-control status 9.9 yr later and to genotype at rs4293393. As a replication set, we tested the genotype association with uromodulin concentration in the Atherosclerosis Risk in Communities (ARIC) Study (n = 42). Geometric means of uromodulin concentrations were 51% higher in case than in control subjects (P = 0.016). The adjusted odds ratio of CKD per 1-SD higher concentration of uromodulin was 1.72 (95% confidence interval 1.07 to 2.77; P = 0.03) after accounting for CKD risk factors and baseline eGFR. We observed lower urinary uromodulin concentrations per each copy of the C allele at rs4293393 in both cohorts. In summary, elevated uromodulin concentrations precede the onset of CKD and associate with a common polymorphism in the UMOD region.

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Uromodulin and Translational Medicine: Will the SNPs Bring Zip to Clinical Practice?

John R. Sedor
J. Am. Soc. Nephrol. 2010 21: 204-206. [Full Text] [PDF]

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				Uromodulin and Translational Medicine: Will the SNPs Bring Zip to Clinical Practice? J. Am. Soc. Nephrol., February 1, 2010; 21(2): 204 - 206.

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673