Title | TCF7L2 variants associate with CKD progression and renal function in population-based cohorts. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Köttgen A, Hwang S-J, Rampersaud E, Coresh J, North KE, Pankow JS, Meigs JB, Florez JC, Parsa A, Levy D, Boerwinkle E, Shuldiner AR, Fox CS, Kao LWH |
Journal | J Am Soc Nephrol |
Volume | 19 |
Issue | 10 |
Pagination | 1989-99 |
Date Published | 2008 Oct |
ISSN | 1533-3450 |
Keywords | Adult, Aged, Chronic Disease, Cohort Studies, Cross-Sectional Studies, Disease Progression, Female, Genotype, Glomerular Filtration Rate, Humans, Kidney Diseases, Male, Middle Aged, Polymorphism, Single Nucleotide, TCF Transcription Factors, Transcription Factor 7-Like 2 Protein |
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 |
DOI | 10.1681/ASN.2007121291 |
Alternate Journal | J Am Soc Nephrol |
PubMed ID | 18650481 |
PubMed Central ID | PMC2551569 |
Grant List | 1K12RR023250-01 / RR / NCRR NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States U01 HL72515 / HL / NHLBI NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States K01DK067207 / DK / NIDDK NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States P30 DK072488 / DK / NIDDK NIH HHS / United States M01 RR016500 / RR / NCRR NIH HHS / United States N01HC55019 / HL / NHLBI NIH HHS / United States K23 DK065978 / DK / NIDDK NIH HHS / United States N01HC55020 / HL / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States K01 DK067207 / DK / NIDDK NIH HHS / United States K12 RR023250 / RR / NCRR NIH HHS / United States T32 HL072751 / HL / NHLBI NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States N01HC55022 / HL / NHLBI NIH HHS / United States M01 RR 16500 / RR / NCRR NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States T32HL072751 / HL / NHLBI NIH HHS / United States M01 RR 000052 / RR / NCRR NIH HHS / United States M01 RR000052 / RR / NCRR NIH HHS / United States K24 DK080140 / DK / NIDDK NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States U01 HL072515 / HL / NHLBI NIH HHS / United States K23 DK65978-03 / DK / NIDDK NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States |