Aug 29, 2012 - divided into Group 1 (9204 patients- normal serial Tn and CKMB): .... Methods: Direct mPTP opening was assessed at 37°C in isolated adult rat car- ...... Kingdom; 2Manchester Academic Health Sciences Centre, Manchester, ...... CARE-HF, COMPANION, CONTAK-CD, MIRACLE, MIRACLE-ICD, MIRACLE-.
Wednesday, 29 August 2012
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Downloaded from http://eurheartj.oxfordjournals.org/ by guest on January 14, 2016
Bench to practice: clues from the genes
BENCH TO PRACTICE: CLUES FROM THE GENES 5184 A blood pressure genetic risk score predicts incident cardiovascular events in 36,950 Finnish individuals V. Salomaa 1 , A.S. Havulinna 1 , J. Kettunen 1 , J. Eriksson 1 , A. Jula 2 , K. Kontula 3 , C. Newton-Cheh 4 . 1 National Institute for Health and Welfare, Helsinki, Finland; 2 National Institute for Health and Welfare, Turku, Finland; 3 University of Helsinki, Department of Medicine, Helsinki, Finland; 4 Massachusetts General Hospital, Center for Human Genetic Research and Cardiovascular Research Center, Boston, United States of America
5185 A variant in the ABO gene explains the variation in soluble E-selectin levels - results from dense-genotyping in two independent populations M. Karakas 1 , J. Baumert 2 , M.E. Kleber 3 , B. Thorand 2 , D. Dallmeier 1 , W. Rottbauer 1 , C. Meisinger 2 , T. Illig 2 , W. Maerz 3 , W. Koenig 1 . 1 University of Ulm, Faculty of Medicine, Department of Internal Medicine II-Cardiology, Ulm, Germany; 2 Helmholtz Center of Munich, Institute of Epidemiology, Neuherberg, Germany; 3 Mannheim Institute of Public Health, Social & Preventive Medicine, Heidelberg University, Mannheim, Germany Background: Elevated soluble (s) E-selectin levels have been associated with various cardiovascular diseases. Recently, genetic variants in the ABO blood group have been related to sE-selectin levels in a small cohort of patients with type 1 diabetes. We evaluated whether this association is reproducible in two large samples of Caucasians. Methods: Data of the present study was drawn from the population-based MONICA/KORA Augsburg study (n = 1,482) and the case-control-based LURIC study (n = 1,546). A high-density genotyping array containing single-nucleotide polymorphisms (SNPs) from E-selectin candidate genes (50K IBC Chip) selected on known biology of E-selectin metabolism, mouse genetic studies, and human genetic association studies, was used for genotyping. Linear regression analyses with adjustment for age and sex were applied to assess associations between gene variants and sE-selectin levels. Results: A number of 12 SNPs (in KORA) and 13 SNPs (in LURIC), all from the ABO blood group gene were significantly associated with levels of logtransformed sE-selectin. The strongest association was observed for rs651007 with a change of log-transformed sE-selectin level per one copy of the minor allele of -0.37 ng/ml (p=1.87x10-103) in KORA and -0.35 ng/ml (p=5.11x10-84) in LURIC. All SNPs had minor allele frequencies above 20% showing a substantial gene variation. Conclusions: Our findings in two independent samples indicate that the genetic variants at the ABO locus affect sE-selectin levels. Since distinct genome wide association studies linked the ABO gene with myocardial infarction in the presence of coronary atherosclerosis and with coronary artery disease, these findings may not only enhance our understanding of adhesion molecule biology, but may also provide a focus for several novel research avenues.
5186 Gene-gene interactions in coronary artery disease M.D. Musameh 1 , W.Y.S. Wang 2 , C.P. Nelson 1 , A.J. Balmforth 3 , S.G. Ball 4 , A.S. Hall 3 , M. Tomaszewski 1 , N.J. Samani 1 . 1 University of Leicester, Department of Cardiovascular Sciences, Leicester, United Kingdom; 2 University of Queensland, Brisbane, Australia; 3 University of Leeds, MCRC, Leeds Institute of Genetics, Health and Therapeutics, Leeds, United Kingdom; 4 University of Leeds, Leeds, United Kingdom Background: Only a small fraction of the heritability of coronary artery disease (CAD) has been explained by common variants identified by genome-wide association studies. Gene-gene interactions could explain some of the missing heritability. Using a custom-built array, we investigated whether interactions between common alleles in genes and pathways of known importance to cardiovascular regulation contributes to the heritability of CAD. Methods: The study population comprise 2101 CAD cases recruited into the British Heart Foundation Family Heart Study and 2426 controls recruited into the Wellcome Trust Case Control Consortium. All cases and controls were of white British origin. The genotyping platform employed was the 50K IBC gene-centric array containing 45707 single nucleotide polymorphisms (SNPs) in ∼ 2100 genes of known biological relevance to cardiovascular system. After applying appropriate quality control filters, 11332 independent (r2 ≤ 0.5), common (minor allele frequency >10%), were included in pair-wise SNP-SNP exhaustive interaction analysis using two stage statistical approach employing logistic regression for additive allelic interaction models (PLINK and INTERSNP software packages). Results: None of the analysed SNP-SNP interactions was statistically significant after correction for multiple testing (P= 7.8 X 10-10). The most significant interaction identified in this analysis was between rs9840469 (FRMD4B) on chromosome 3 and rs10911935 (PLA2G4A) on chromosome 1 (P= 4.63 X 10-7). Analysis of subsets of SNPs pre-selected based on their nominal association with CAD (p
