Peter Rock

Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.

TCF7L2 variants associate with CKD progression and renal function in population-based cohorts.

Anna Köttgen; Shih-Jen Hwang; Evadnie Rampersaud; Josef Coresh; Kari E North; James S Pankow; James B Meigs; Jose C Florez; Afshin Parsa; Daniel Levy; et al. (Profiled Authors: Afshin Parsa; Alan R Shuldiner)

Department of Epidemiology and Welch Center for Prevention, Epidemiology & Clinical Research, Johns Hopkins University, Baltimore, Maryland, USA.
Journal of the American Society of Nephrology : JASN 2008;19(10):1989-99.

Genetic variants may increase susceptibility to both diabetes and kidney disease. Whether known diabetes-associated variants in the transcription factor 7-like 2 (TCF7L2) gene are associated with chronic kidney disease (CKD) progression and markers of kidney function is unknown. Participants of the Atherosclerosis Risk in Communities Study (ARIC; n = 11,061 self-identified white and n = 4014 black), Framingham Heart Offspring Cohort (FHS; n = 2468), and Heredity and Phenotype Intervention Heart Study (HAPI; n = 861) were genotyped at five (ARIC) and two (FHS) common TCF7L2 variants. The diabetes-conferring risk alleles at rs7903146 and rs7901695 were significantly associated with CKD progression among ARIC participants overall and among those without baseline diabetes. The overall adjusted hazard ratios per rs7903146 T allele were 1.17 (95% confidence interval [CI] 1.04 to 1.32) for white individuals and 1.20 (95% CI 1.03 to 1.41) for black individuals. Similarly, the overall hazard ratios per rs7901695 C allele were 1.19 (95% CI 1.06 to 1.34) for white individuals and 1.27 (95% CI 1.09 to 1.48) for black individuals. The FHS cohort supported these results: The rs7903146 T allele was significantly associated with lower estimated GFR (P = 0.01) and higher cystatin C (P = 0.004) in adjusted analyses overall and among those without diabetes. In the HAPI cohort, the rs7901695 C allele was significantly associated with lower estimated GFR in adjusted analyses (P = 0.049), as were several variants upstream and downstream of TCF7L2 (P < 0.003). No identified variant in the ARIC or FHS cohorts was associated with albuminuria. In conclusion, several population-based samples suggest that variants in the TCF7L2 gene are associated with reduced kidney function or CKD progression, overall and specifically among participants without diabetes.

6 Originating Grant

• 1.

  Shuldiner, Alan R

  Clinical Research Career Development (RMI)

  23 September 2005 - 31 July 2010

  NATIONAL CENTER FOR RESEARCH RESOURCES

• 2.

  SHULDINER, ALAN R.

  Mid-Atlantic Nutrition Obesity Research Center

  15 September 2005 - 31 August 2015

  NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

• 3.

  Pallone, Thomas L

  Training Grant in Cardiac and Vascular Cell Biology

  1 April 2003 - 31 March 2008

  NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

• 4.

  STANLEY, WILLIAM C

  Training Grant in Cardiac and Vascular Cell Biology

  1 April 2003 - 31 July 2014

  NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

• 5.

  Shuldiner, Alan R

  Genome-wide Search for CVD Gene-Environment Interactions

  30 September 2002 - 31 May 2009

  NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

• 6.

  Reece, E Albert

  General Clinical Research Center

  1 March 2002 - 30 June 2010

  NATIONAL CENTER FOR RESEARCH RESOURCES

Scientific Context

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