Dataset Information

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

ABSTRACT:

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.

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.

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.

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.

SUBMITTER: Verschuren JJ

PROVIDER: S-EPMC3574159 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

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

Verschuren Jeffrey J W JJ Trompet Stella S Deelen Joris J Stott David J DJ Sattar Naveed N Buckley Brendan M BM Ford Ian I Heijmans Bastiaan T BT Guchelaar Henk-Jan HJ Houwing-Duistermaat Jeanine J JJ Slagboom P Eline PE Jukema J Wouter JW

PloS one 20130215 2

<h4>Purpose</h4>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.<h4>Methods</h4>The PLIN ...[more]

PMID: 23457540

Similar Datasets

Project description:The proposal aims to characterise the pathways of DSB repair and recombination in Arabidopsis with the main focus of this research being the NHEJ pathway of illegitimate recombination. We will build on our expertise and resources in the field of DSB repair in plants, using the Arabidopsis NHEJ mutant atku80 which is an excellent model system for the study of DSB repair in higher eukaryotes (West et al., 2002 Plant J. 31, 517-28). Comparison of the transcriptome in NHEJ mutant and wild type plants under different experimental conditions will identify novel candidate genes involved in DNA DSB repair or damage signalling pathways.We will conduct 4 separate experiments on Arabidopsis seedlings grown on 0.5 MS media: the first will be a control consisting of Wassilewskija (WS-2) plants grown under standard conditions. In the second experiment WS plants will be exposed to the chemotherapeutic agent bleomycin (1 microgram per ml). This agent has been shown to cause both single and double strand breaks in the genome of Arabidopsis seedlings (Menke et al., 2001 Mut. Res. 493, 87-93). This agent is used in preference to gamma irradiation, which causes high levels of oxidative damage to cellular components. These experiments will characterise for the first time the transcriptional responses of Arabidopsis cells to the specific induction of DNA strand breaks. The transcript profile will also be determined in untreated atku80 mutants. This experiment will identify the components of novel and previously characterised DNA repair pathways up regulated in the mutant background. Finally, transcript analysis of bleomycin treated atku80 mutants and comparison with untreated mutant plants and both untreated and treated WS plants will identify novel putative DSB repair genes up regulated in response to genotoxic stress in the absence of a Ku80 mediated DSB repair pathway.The results of these studies will provide new and important information which will be instrumental in identifying novel genes and pathways involved in DNA repair and genome stability in plants and help elucidate the fundamental differences that exist between animal and plant DSB repair processes. Experiment Overall Design: Number of plants pooled:20

Dataset Information

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

Purpose

Methods

Results

Conclusion

Publications

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

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