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

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 Hunt

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.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.

Original languageEnglish
Pages (from-to)552-558
Number of pages7
JournalAmerican Journal of Hypertension
Volume22
Issue number5
DOIs
Publication statusPublished - May 2009
Externally publishedYes

Fingerprint

Molecular Epidemiology
Cell Cycle Checkpoints
Glomerular Filtration Rate
Atherosclerosis
African Americans
Blood Pressure
Kidney
Hypertension
Genes
DNA Damage
Single Nucleotide Polymorphism
Cell Cycle Proteins
Genetic Models
Wounds and Injuries
Kidney Diseases
Transducers
Type 2 Diabetes Mellitus
Meta-Analysis
Apoptosis

ASJC Scopus subject areas

  • Internal Medicine

Cite this

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. / Franceschini, Nora; North, Kari E.; Arnett, Donna; Pankow, James S.; Chung, Jay H.; Baird, Lisa; Leppert, Mark F.; Eckfeldt, John H.; Boerwinkle, Eric; Gu, C. Charles; Lewis, Cora E.; Myers, Richard H.; Turner, Stephen T.; Weder, Alan; Kao, W. H Linda; Mosley, Thomas H.; Chakravarti, Aravinda; Kramer, Holly; Zhang, Jinghui; Hunt, Steven.

In: American Journal of Hypertension, Vol. 22, No. 5, 05.2009, p. 552-558.

Research output: Contribution to journalArticle

Franceschini, 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, WHL, Mosley, TH, Chakravarti, A, Kramer, H, Zhang, J & Hunt, S 2009, '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', American Journal of Hypertension, vol. 22, no. 5, pp. 552-558. https://doi.org/10.1038/ajh.2009.41
Franceschini, Nora ; North, Kari E. ; Arnett, Donna ; Pankow, James S. ; Chung, Jay H. ; Baird, Lisa ; Leppert, Mark F. ; Eckfeldt, John H. ; Boerwinkle, Eric ; Gu, C. Charles ; Lewis, Cora E. ; Myers, Richard H. ; Turner, Stephen T. ; Weder, Alan ; Kao, W. H Linda ; Mosley, Thomas H. ; Chakravarti, Aravinda ; Kramer, Holly ; Zhang, Jinghui ; Hunt, Steven. / 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. In: American Journal of Hypertension. 2009 ; Vol. 22, No. 5. pp. 552-558.
@article{8eabd6adf2bf4a678d74aa19eaffcbd9,
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.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.",
author = "Nora Franceschini and North, {Kari E.} and Donna Arnett and Pankow, {James S.} and Chung, {Jay H.} and Lisa Baird and Leppert, {Mark F.} and Eckfeldt, {John H.} and Eric Boerwinkle and Gu, {C. Charles} and Lewis, {Cora E.} and Myers, {Richard H.} and Turner, {Stephen T.} and Alan Weder and Kao, {W. H Linda} and Mosley, {Thomas H.} and Aravinda Chakravarti and Holly Kramer and Jinghui Zhang and Steven Hunt",
year = "2009",
month = "5",
doi = "10.1038/ajh.2009.41",
language = "English",
volume = "22",
pages = "552--558",
journal = "American Journal of Hypertension",
issn = "0895-7061",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - The association of cell cycle checkpoint 2 variants and kidney function

T2 - Findings of the family blood pressure program and the atherosclerosis risk in communities study

AU - Franceschini, Nora

AU - North, Kari E.

AU - Arnett, Donna

AU - Pankow, James S.

AU - Chung, Jay H.

AU - Baird, Lisa

AU - Leppert, Mark F.

AU - Eckfeldt, John H.

AU - Boerwinkle, Eric

AU - Gu, C. Charles

AU - Lewis, Cora E.

AU - Myers, Richard H.

AU - Turner, Stephen T.

AU - Weder, Alan

AU - Kao, W. H Linda

AU - Mosley, Thomas H.

AU - Chakravarti, Aravinda

AU - Kramer, Holly

AU - Zhang, Jinghui

AU - Hunt, Steven

PY - 2009/5

Y1 - 2009/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=67349148561&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67349148561&partnerID=8YFLogxK

U2 - 10.1038/ajh.2009.41

DO - 10.1038/ajh.2009.41

M3 - Article

C2 - 19265784

AN - SCOPUS:67349148561

VL - 22

SP - 552

EP - 558

JO - American Journal of Hypertension

JF - American Journal of Hypertension

SN - 0895-7061

IS - 5

ER -