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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.

TitleThe association of cell cycle checkpoint 2 variants and kidney function: findings of the Family Blood Pressure Program and the Atherosclerosis Risk In Communities study.
Publication TypeJournal Article
Year of Publication2009
AuthorsFranceschini N, North KE, Arnett D, Pankow JS, Chung JH, Baird L, Leppert MF, Eckfeldt JH, Boerwinkle E, Gu CC, Lewis CE, Myers RH, Turner ST, Weder A, Kao LWH, Mosley TH, Chakravarti A, Kramer H, Zhang J, Hunt SC
JournalAm J Hypertens
Volume22
Issue5
Pagination552-8
Date Published2009 May
ISSN1941-7225
KeywordsAdult, African Americans, Aged, Atherosclerosis, Blood Pressure, Checkpoint Kinase 2, DNA Damage, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Humans, Hypertension, Kidney Diseases, Male, Middle Aged, Polymorphism, Single Nucleotide, Prospective Studies, Protein-Serine-Threonine Kinases, Risk
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.

DOI10.1038/ajh.2009.41
Alternate JournalAm J Hypertens
PubMed ID19265784
PubMed Central IDPMC2727134
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
U01 HL054509 / HL / NHLBI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
U01 HL054509-10 / HL / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States