Non-Homologous End-Joining Pathway Associated with Occurrence of Myocardial Infarction: Gene Set Analysis of Genome-Wide Association Study Data

Verschuren, Jeffrey J. W.; Trompet, Stella; Deelen, Joris; Stott, David J.; Sattar, Naveed; Buckley, Brendan M.; Ford, Ian; Heijmans, Bastiaan T.; Guchelaar, Henk-Jan; Houwing-Duistermaat, Jeanine J.; Slagboom, P. Eline; Jukema, J. Wouter
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
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.


Related Articles

  • Association of Polymorphic Marker A1/A2 of Gene ITGB3 with Coronary Artery Disease and Myocardial Infarction. Tchoudakova, D. A.; Minushkina, L. O.; Zateyshchikov, D. A.; Nosikov, V. V. // Russian Journal of Genetics;Oct2004, Vol. 40 Issue 10, p1156 

    The distributions of the alleles and genotypes of polymorphic marker A1/A2 of gene ITGB3 encoding the β3 subunit of integrin αIIbβ3 in groups of patients with coronary artery disease (CAD), including those who have had myocardial infarction (MI), and in the control group have been...

  • Dose-dependent effects of thyroid hormone on post-ischemic cardiac performance: potential involvement of Akt and ERK signalings. Mourouzis, Iordanis; Mantzouratou, Polixeni; Galanopoulos, Georgios; Kostakou, Erietta; Roukounakis, Nikolaos; Kokkinos, Alexandros; Cokkinos, Dennis; Pantos, Constantinos // Molecular & Cellular Biochemistry;Apr2012, Vol. 363 Issue 1/2, p235 

    The present study explored the effects of thyroid hormone (TH) treatment on post-ischemic cardiac function and potential implicated mechanisms. Acute myocardial infarction (AMI) was induced in mice by coronary artery ligation while sham-operated animals served as controls. This procedure...

  • Behind The Headlines: Coffee's effect on MI risk is genetic. Simonite, Tom // GP: General Practitioner;3/17/2006, p29 

    The article discusses media reports which describes that drinking more than three cups of coffee increases the risk of a heart attack. Around a third of the British population might carry the ∗1F gene and, if they drink more than three cups of coffee a day, their risk of myocardial...

  • Polymorphism of the Apolipoprotein E Gene and Risk of Myocardial Infarction. Mustafina, O. E.; Shagisultanova, E. I.; Tuktarova, I. A.; Khusnutdinova, E. K. // Molecular Biology;Nov2002, Vol. 36 Issue 6, p792 

    The apolipoprotein E (ApoE) gene polymorphism resulting from nucleotide substitutions in exon 4 was analyzed in Russian and Tatar patients with myocardial infarction (MI) from Bashkortostan. Alleles ℇ2, ℇ3, and ℇ4 were identified by PCR. The genotype frequency distribution...

  • Myocardial transfection of hypoxia-inducible factor-1α and co-transplantation of mesenchymal stem cells enhance cardiac repair in rats with experimental myocardial infarction. Bingqing Huang; Juying Qian; Jianying Ma; Zheyong Huang; Yunli Shen; Xueying Chen; Aijun Sun; Junbo Ge; Haozhu Chen // Stem Cell Research & Therapy;2014, Vol. 5 Issue 1, p1 

    Introduction Mesenchymal stem cells (MSCs) have potential for the treatment of myocardial infarction. However, several meta-analyses revealed that the outcome of stem cell transplantation is dissatisfactory. A series of studies demonstrated that the combination of cell- and gene therapy was a...

  • Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors. Jagtap, Prakash; Szabó, Csaba // Nature Reviews Drug Discovery;May2005, Vol. 4 Issue 5, p421 

    Poly(ADP-ribose) polymerases (PARPs) are involved in the regulation of many cellular functions. Three consequences of the activation of PARP1, which is the main isoform of the PARP family, are particularly important for drug development: first, its role in DNA repair; second, its capacity to...

  • Ischemic postconditioning: mechanisms, comorbidities, and clinical application. Buchholz, Bruno; Donato, Martín; D'Annunzio, Verónica; Gelpi, Ricardo // Molecular & Cellular Biochemistry;Jul2014, Vol. 392 Issue 1/2, p1 

    Since ischemic heart disease (IHD) is a major cause of mortality and heart failure, novel therapeutic strategies are expected to improve the clinical outcomes of patients with acute myocardial infarction. Brief episodes of ischemia/reperfusion performed at the onset of reperfusion can reduce...

  • Genetic Variants Associated with Myocardial Infarction and the Risk Factors in Chinese Population. Wang, Yongqin; Wang, Lefeng; Liu, Xin; Zhang, Yongzhi; Yu, Liping; Zhang, Fan; Liu, Lisheng; Cai, Jun; Yang, Xinchun; Wang, Xingyu // PLoS ONE;Jan2014, Vol. 9 Issue 1, p1 

    Background: Recent genome-wide association (GWA) studies in Caucasians identified multiple single nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD). The associations of those SNPs with myocardial infarction (MI) have not been replicated in Asian populations. Among...

  • Modeling radiation effects at the tissue level. Müller, M.; Durante, M.; Stöcker, H.; Merz, F.; Bechmann, I. // European Physical Journal D -- Atoms, Molecules, Clusters & Opti;Nov2010, Vol. 60 Issue 1, p171 

    For the understanding of radiation action in humans, a synergistic approach of experiments and quantitative modeling of working hypotheses is necessary. A large set of experimental data at the single-cell level are available, and biophysical modeling of radiation action has so far mostly...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics