title: 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.
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.
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. noraf@unc.edu
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.forename: Donna
authors.initials: D
authors.lastname: Arnett
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
authors.forename: Jay H
authors.initials: JH
authors.lastname: Chung
authors.forename: Lisa
authors.initials: L
authors.lastname: Baird
authors.forename: Mark F
authors.initials: MF
authors.lastname: Leppert
authors.forename: John H
authors.initials: JH
authors.lastname: Eckfeldt
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: C Charles
authors.initials: CC
authors.lastname: Gu
authors.forename: Cora E
authors.initials: CE
authors.lastname: Lewis
authors.forename: Richard H
authors.initials: RH
authors.lastname: Myers
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Turner
authors.forename: Alan
authors.initials: A
authors.lastname: Weder
authors.forename: W H Linda
authors.initials: WH
authors.lastname: Kao
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Mosley
authors.forename: Aravinda
authors.initials: A
authors.lastname: Chakravarti
authors.forename: Holly
authors.initials: H
authors.lastname: Kramer
authors.forename: Jinghui
authors.initials: J
authors.lastname: Zhang
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hunt
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D050197:Atherosclerosis / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics; D064447:Checkpoint Kinase 2; D004249:DNA Damage / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000235:genetics; D007674:Kidney Diseases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012306:Risk; D044465:White People / Q000235:genetics
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases