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.
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.
Franceschini
Nora
N
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. noraf@unc.edu
North
Kari E
KE
Arnett
Donna
D
Pankow
James S
JS
Chung
Jay H
JH
Baird
Lisa
L
Leppert
Mark F
MF
Eckfeldt
John H
JH
Boerwinkle
Eric
E
Gu
C Charles
CC
Lewis
Cora E
CE
Myers
Richard H
RH
Turner
Stephen T
ST
Weder
Alan
A
Kao
W H Linda
WH
Mosley
Thomas H
TH
Chakravarti
Aravinda
A
Kramer
Holly
H
Zhang
Jinghui
J
Hunt
Steven C
SC
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
D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases