The Association of Cell Cycle Checkpoint 2 Variants and Kidney Function: Findings of the Family Blood Pressure Program and the Atherosclerosis Risk in Communities Study
Year: 2009
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Recent experimental evidence suggests that DNA damage and cell cycle regulatory proteins are involved in kidney injury and apoptosis. The checkpoint 2 gene (CHEK2) is an important transducer in DNA damage signaling pathways in response to injury, and therefore, CHEK2 variants may affect susceptibility to kidney disease. METHODS: We used tag-single-nucleotide polymorphisms (tag-SNPs) to evaluate the association of the CHEK2 with kidney function (estimated glomerular filtration rate, eGFR) in 1,549 African-American and 1,423 white Hypertension Genetic Epidemiology Network (HyperGEN) participants. We performed replication analyses in the Genetic Epidemiology Network of Arteriopathy (GENOA) participants (1,746 African Americans and 1,418 whites), GenNet participants (706 whites), and Atherosclerosis Risk in Communities (ARIC) study participants (3,783 African Americans and 10,936 whites). All analyses were race-stratified and used additive genetic models with adjustments for covariates and for family structure, if needed. RESULTS: One tag-SNP, rs5762764, was associated with eGFR in HyperGEN (P = 0.003) and GENOA white participants (P = 0.009), and it was significantly associated with eGFR in meta-analyses (P = 0.002). The associations were independent of type 2 diabetes. CONCLUSIONS: These results suggest that CHEK2 variants may influence eGFR in the context of hypertension.
Source: American Journal of Hypertension
DOI: 10.1038/ajh.2009.41
Authors: Nora Franceschini, Kari E. North, Donna Arnett, James S. Pankow, Jay H. Chung, Lisa Baird, Mark F. Leppert, John H. Eckfeldt, Eric Boerwinkle, C. Charles Gu, Cora E. Lewis, Richard H. Myers, Stephen T. Turner, Alan Weder, W.H. Linda Kao, Thomas H. Mosley, Aravinda Chakravarti, Holly Kramer, Jinghui Zhang, Steven C. Hunt
Institutions: University of North Carolina at Chapel Hill, University of Alabama at Birmingham, University of Minnesota, National Heart, Lung, and Blood Institute, University of Utah, The University of Texas Health Science Center at Houston, Washington University in St. Louis, Boston University, Mayo Clinic, University of Michigan, Michigan Medicine, Johns Hopkins University, University of Mississippi Medical Center, Johns Hopkins Medicine, Loyola University Chicago, Loyola Medicine, National Institutes of Health, National Cancer Institute
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Awards: G118440752, G1325221871, G136105103, Atherosclerosis Risk in Communities Study (ARIC), G215333750, CCSP FIELD CENTER, G25881238, COMMUNITY AND COHORT SURVEILLANCE PROGRAM, CENTRAL HEMOSTATIS LABORATORY FOR CCSP, G3236609591, G390162502, Atherosclerosis Risk in Communities Study (ARIC), G528395701, G5451084504, Atherosclerosis Risk in Communities Study (ARIC), G6203107232, G7518182772, G786153652, G793702358, G812579647, G8486527673, Atherosclerosis Risk in Communities Study (ARIC)
OpenAlex ID: W2127966801