Non-homologous end-joining pathway associated with occurrence of myocardial infarction: gene set analysis of genome-wide association study data

Verschuren, J.J.W. et al. (2013) Non-homologous end-joining pathway associated with occurrence of myocardial infarction: gene set analysis of genome-wide association study data. PLoS ONE, 8(2), e56262. (doi:10.1371/journal.pone.0056262) (PMID:23457540) (PMCID:PMC3574159)

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Abstract

<p>Purpose: DNA repair deficiencies have been postulated to play a role in the development and progression of cardiovascular disease (CVD). The hypothesis is that DNA damage accumulating with age may induce cell death, which promotes formation of unstable plaques. Defects in DNA repair mechanisms may therefore increase the risk of CVD events. We examined whether the joints effect of common genetic variants in 5 DNA repair pathways may influence the risk of CVD events.</p> <p>Methods: The PLINK set-based test was used to examine the association to myocardial infarction (MI) of the DNA repair pathway in GWAS data of 866 subjects of the GENetic DEterminants of Restenosis (GENDER) study and 5,244 subjects of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. We included the main DNA repair pathways (base excision repair, nucleotide excision repair, mismatch repair, homologous recombination and non-homologous end-joining (NHEJ)) in the analysis.</p> <p>Results: The NHEJ pathway was associated with the occurrence of MI in both GENDER (P = 0.0083) and PROSPER (P = 0.014). This association was mainly driven by genetic variation in the MRE11A gene (PGENDER = 0.0001 and PPROSPER = 0.002). The homologous recombination pathway was associated with MI in GENDER only (P = 0.011), for the other pathways no associations were observed.</p> <p>Conclusion: This is the first study analyzing the joint effect of common genetic variation in DNA repair pathways and the risk of CVD events, demonstrating an association between the NHEJ pathway and MI in 2 different cohorts.</p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stott, Professor David J and Ford, Professor Ian and Sattar, Professor Naveed
Authors: Verschuren, J.J.W., Trompet, S., Deelen, J., Stott, D.J., Sattar, N., Buckley, B.M., Ford, I., Heijmans, B.T., Guchelaar, H.-J., Houwing-Duistermaat, J.J., Slagboom, P.E., and Jukema, J.W.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
Published Online:15 February 2013
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in PLoS ONE 8(2):e56262
Publisher Policy:Reproduced under a Creative Commons License

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