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, Eric Boerwinkle, Alan R. Shuldiner, Caroline S. Fox, W. H.Linda Kao

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33 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1989-1999
Number of pages11
JournalJournal of the American Society of Nephrology
Volume19
Issue number10
DOIs
StatePublished - Oct 1 2008

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ASJC Scopus subject areas

  • Nephrology

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Köttgen, A., Hwang, S. J., Rampersaud, E., Coresh, J., North, K. E., Pankow, J. S., Meigs, J. B., Florez, J. C., Parsa, A., Levy, D., Boerwinkle, E., Shuldiner, A. R., Fox, C. S., & Kao, W. H. L. (2008). TCF7L2 variants associate with CKD progression and renal function in population-based cohorts. Journal of the American Society of Nephrology, 19(10), 1989-1999. https://doi.org/10.1681/ASN.2007121291