Genetic variation in the SMARCA2 gene is associated with cardiovascular events

Verschuren, J.J.W., Wessels, J.A., Trompet, S., Stott, D.J. , Sattar, N. , Buckley, B., Guchelaar, H.-J. and Jukema, J. (2012) Genetic variation in the SMARCA2 gene is associated with cardiovascular events. Journal of the American College of Cardiology, 59(13), E1393. (doi: 10.1016/S0735-1097(12)61394-1)

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<p>Background: 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 induces cell death that promotes formation of unstable plaques. Using a DNA repair pathway approach we systematically examined whether common genetic variation in DNA excision repair genes influenced the risk of cardiovascular events.</p> <p>Methods: The DNA biobank from 5,244 subjects of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) was studied. Cases were defined as patients with fatal/non-fatal myocardial infarction or stroke (N=1,714) and were compared to controls without events (N=3,530). DNA excision repair genes were selected using a systematic pathway approach. A total of 38 single nucleotide polymorphisms (SNPs) within 14 genes were selected. Genotyping was performed using Illumina Human 660-Quad Beadchips. Associations were tested with logistic regression and multi testing correction was applied.</p> <p>Results: A polymorphism in the SMARCA2 gene (rs9298820) was associated with an increased risk of events, OR 1.14 (95% CI 1.05-1.25), p=0.002. Inspection of the genomic region of SMARCA2 revealed 6 independent loci associated with the endpoint, of which the strongest association was found with rs3793516, OR 1.18 (1.08-1.30), p=0.0002. A risk score of the 6 SNPs demonstrated a solid association with cardiovascular events, OR 1.13 (1.07-1.19), p= 9.0E-6.</p> <p>Conclusions: In this explorative study we found an association of cardiovascular events and genetic variation in the SMARCA2 gene, a gene involved in chromatin remodelling. The fact that several loci within the gene were associated and the risk score showed a strong association, increases the likelihood of causal involvement of this gene. These hypotheses-generating findings require extension by replication and functional analysis.</p>

Item Type:Articles
Glasgow Author(s) Enlighten ID:Stott J, Professor David and Sattar, Professor Naveed
Authors: Verschuren, J.J.W., Wessels, J.A., Trompet, S., Stott, D.J., Sattar, N., Buckley, B., Guchelaar, H.-J., and Jukema, J.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Journal of the American College of Cardiology
Publisher:Elsevier Inc.

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