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.MethodsWe 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.ResultsOne 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.ConclusionsThese results suggest that CHEK2 variants may influence eGFR in the context of hypertension.
Bibliographical noteFunding Information:
National Heart, Lung, and Blood Institute: Dina Paltoo and Cashell E. Jaquish. Web site: http://www.biostat.wustl.edu/fbpp/FBPP.shtml The atherosclerosis Risk in Communities (aRIC) Study is carried out as a collaborative study supported by the National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022. We thank the staff and participants of the aRIC study for their important contributions.The work was also supported by the american Heart association no. 0675001N (N.F.).