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

TitleTCF7L2 variants associate with CKD progression and renal function in population-based cohorts.
Publication TypeJournal Article
Year of Publication2008
AuthorsKöttgen 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
JournalJ Am Soc Nephrol
Volume19
Issue10
Pagination1989-99
Date Published2008 Oct
ISSN1533-3450
KeywordsAdult, 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

DOI10.1681/ASN.2007121291
Alternate JournalJ Am Soc Nephrol
PubMed ID18650481
PubMed Central IDPMC2551569
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
1K12RR023250-01 / RR / NCRR NIH HHS / United States
K01 DK067207 / DK / NIDDK NIH HHS / United States
K12 RR023250 / 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
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
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
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
M01 RR016500 / RR / NCRR NIH HHS / United States
N01HC55019 / 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
K23 DK065978 / DK / NIDDK NIH HHS / United States