Variation in the checkpoint kinase 2 gene is associated with type 2 diabetes in multiple populations View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-12

AUTHORS

Kari E. North, Nora Franceschini, Christy L. Avery, Lisa Baird, Mariaelisa Graff, Mark Leppert, Jay H. Chung, Jinghui Zhang, Craig Hanis, Eric Boerwinkle, Kelly A. Volcik, Megan L. Grove, Thomas H. Mosley, Charles Gu, Gerardo Heiss, James S. Pankow, David J. Couper, Christie M. Ballantyne, W. H. Linda Kao, Alan B. Weder, Richard S. Cooper, Georg B. Ehret, Ashley A. O’Connor, Aravinda Chakravarti, Steven C. Hunt

ABSTRACT

Identification and characterization of the genetic variants underlying type 2 diabetes susceptibility can provide important understanding of the etiology and pathogenesis of type 2 diabetes. We previously identified strong evidence of linkage for type 2 diabetes on chromosome 22 among 3,383 Hypertension Genetic Epidemiology Network (HyperGEN) participants from 1,124 families. The checkpoint 2 (CHEK2) gene, an important mediator of cellular responses to DNA damage, is located 0.22 Mb from this linkage peak. In this study, we tested the hypothesis that the CHEK2 gene contains one or more polymorphic variants that are associated with type 2 diabetes in HyperGEN individuals. In addition, we replicated our findings in two other Family Blood Pressure Program (FBPP) populations and in the population-based Atherosclerosis Risk in Communities (ARIC) study. We genotyped 1,584 African-American and 1,531 white HyperGEN participants, 1,843 African-American and 1,569 white GENOA participants, 871 African-American and 1,009 white GenNet participants, and 4,266 African-American and 11,478 white ARIC participants for four single nucleotide polymorphisms (SNPs) in CHEK2. Using additive models, we evaluated the association of CHEK2 SNPs with type 2 diabetes in participants within each study population stratified by race, and in a meta-analysis, adjusting for age, age(2), sex, sex-by-age interaction, study center, and relatedness. One CHEK2 variant, rs4035540, was associated with an increased risk of type 2 diabetes in HyperGEN participants, two replication samples, and in the meta-analysis. These results may suggest a new pathway in the pathogenesis of type 2 diabetes that involves pancreatic beta-cell damage and apoptosis. More... »

PAGES

199-207

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00592-009-0162-z

DOI

http://dx.doi.org/10.1007/s00592-009-0162-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1040248921

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19855918


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470 https://www.grid.ac/institutes/grid.214458.e schema:alternateName University of Michigan–Ann Arbor
471 schema:name Division of Hypertension, University of Michigan School of Medicine, Ann Arbor, MI, USA
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473 https://www.grid.ac/institutes/grid.223827.e schema:alternateName University of Utah
474 schema:name Department of Human Genetics, University of Utah, Salt Lake City, UT, USA
475 Division of Cardiovascular Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA
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478 schema:name Human Genetics Center, University of Texas Health Sciences Center, Houston, TX, USA
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480 https://www.grid.ac/institutes/grid.279885.9 schema:alternateName National Heart Lung and Blood Institute
481 schema:name Laboratory of Biochemical Genetics, National Heart Lung and Blood Institute, Bethesda, MD, USA
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484 schema:name Section of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
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486 https://www.grid.ac/institutes/grid.410711.2 schema:alternateName University of North Carolina System
487 schema:name Carolina Center for Genome Sciences, University of North Carolina, 137 E. Franklin St., Suite 306, 27516, Chapel Hill, NC, USA
488 Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA
489 Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA
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491 https://www.grid.ac/institutes/grid.410721.1 schema:alternateName University of Mississippi Medical Center
492 schema:name Department of Medicine (Geriatrics), University of Mississippi Medical Center, Jackson, MS, USA
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494 https://www.grid.ac/institutes/grid.4367.6 schema:alternateName Washington University in St. Louis
495 schema:name Division of Biostatistics and Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA
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