caa a22 4500 445861487 CHVBK 20180317145444.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s00439-011-0959-z doi (NATIONALLICENCE)springer-10.1007/s00439-011-0959-z Polymorphic variants in tenascin-C ( TNC ) are associated with atherosclerosis and coronary artery disease [Elektronische Daten] [Mollie Minear, David Crosslin, Beth Sutton, Jessica Connelly, Sarah Nelson, Shera Gadson-Watson, Tianyuan Wang, David Seo, Jeffrey Vance, Michael Sketch Jr., Carol Haynes, Pascal Goldschmidt-Clermont, Svati Shah, William Kraus, Elizabeth Hauser, Simon Gregory] Tenascin-C (TNC) is an extracellular matrix protein implicated in biological processes important for atherosclerotic plaque development and progression, including smooth muscle cell migration and proliferation. Previously, we observed differential expression of TNC in atherosclerotic aortas compared with healthy aortas. The goal of this study was to investigate whether common genetic variation within TNC is associated with risk of atherosclerosis and coronary artery disease (CAD) in three independent datasets. We genotyped 35 single nucleotide polymorphisms (SNPs), including 21 haplotype tagging SNPs, in two of these datasets: human aorta tissue samples (n=205) and the CATHGEN cardiovascular study (n=1,325). Eleven of these 35 SNPs were then genotyped in a third dataset, the GENECARD family study of early-onset CAD (n=879 families). Three SNPs representing a block of linkage disequilibrium, rs3789875, rs12347433, and rs4552883, were significantly associated with atherosclerosis in multiple datasets and demonstrated consistent, but suggestive, genetic effects in all analyses. In combined analysis rs3789875 and rs12347433 were statistically significant after Bonferroni correction for 35 comparisons, p=2×10−6 and 5×10−6, respectively. The SNP rs12347433 is a synonymous coding SNP and may be biologically relevant to the mechanism by which tenascin-C influences the pathophysiology of CAD and atherosclerosis. This is the first report of genetic association between polymorphisms in TNC and atherosclerosis or CAD. Springer-Verlag, 2011 Minear Mollie Center for Human Genetics, Duke University Medical Center, 905 S. La Salle Street DUMC 3445, 27710, Durham, NC, USA aut Crosslin David Department of Biostatistics, University of Washington, Seattle, WA, USA aut Sutton Beth School of Pharmacy, Campbell University, Morrisville, NC, USA aut Connelly Jessica Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA aut Nelson Sarah Department of Biostatistics, University of Washington, Seattle, WA, USA aut Gadson-Watson Shera Center for Human Genetics, Duke University Medical Center, 905 S. La Salle Street DUMC 3445, 27710, Durham, NC, USA aut Wang Tianyuan Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA aut Seo David Miller School of Medicine, University of Miami, Miami, FL, USA aut Vance Jeffrey Miller School of Medicine, University of Miami, Miami, FL, USA aut Sketch Jr. Michael Department of Medicine, Duke University Medical Center, Durham, NC, USA aut Haynes Carol Center for Human Genetics, Duke University Medical Center, 905 S. La Salle Street DUMC 3445, 27710, Durham, NC, USA aut Goldschmidt-Clermont Pascal Miller School of Medicine, University of Miami, Miami, FL, USA aut Shah Svati Center for Human Genetics, Duke University Medical Center, 905 S. La Salle Street DUMC 3445, 27710, Durham, NC, USA aut Kraus William Department of Medicine, Duke University Medical Center, Durham, NC, USA aut Hauser Elizabeth Center for Human Genetics, Duke University Medical Center, 905 S. La Salle Street DUMC 3445, 27710, Durham, NC, USA aut Gregory Simon Center for Human Genetics, Duke University Medical Center, 905 S. La Salle Street DUMC 3445, 27710, Durham, NC, USA aut Human Genetics Springer-Verlag 129/6(2011-06-01), 641-654 0340-6717 129:6<641 2011 129 439 https://doi.org/10.1007/s00439-011-0959-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-011-0959-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Minear Mollie Center for Human Genetics, Duke University Medical Center, 905 S. La Salle Street DUMC 3445, 27710, Durham, NC, USA aut NATIONALLICENCE 700 1- Crosslin David Department of Biostatistics, University of Washington, Seattle, WA, USA aut NATIONALLICENCE 700 1- Sutton Beth School of Pharmacy, Campbell University, Morrisville, NC, USA aut NATIONALLICENCE 700 1- Connelly Jessica Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA aut NATIONALLICENCE 700 1- Nelson Sarah Department of Biostatistics, University of Washington, Seattle, WA, USA aut NATIONALLICENCE 700 1- Gadson-Watson Shera Center for Human Genetics, Duke University Medical Center, 905 S. La Salle Street DUMC 3445, 27710, Durham, NC, USA aut NATIONALLICENCE 700 1- Wang Tianyuan Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA aut NATIONALLICENCE 700 1- Seo David Miller School of Medicine, University of Miami, Miami, FL, USA aut NATIONALLICENCE 700 1- Vance Jeffrey Miller School of Medicine, University of Miami, Miami, FL, USA aut NATIONALLICENCE 700 1- Sketch Jr Michael Department of Medicine, Duke University Medical Center, Durham, NC, USA aut NATIONALLICENCE 700 1- Haynes Carol Center for Human Genetics, Duke University Medical Center, 905 S. La Salle Street DUMC 3445, 27710, Durham, NC, USA aut NATIONALLICENCE 700 1- Goldschmidt-Clermont Pascal Miller School of Medicine, University of Miami, Miami, FL, USA aut NATIONALLICENCE 700 1- Shah Svati Center for Human Genetics, Duke University Medical Center, 905 S. La Salle Street DUMC 3445, 27710, Durham, NC, USA aut NATIONALLICENCE 700 1- Kraus William Department of Medicine, Duke University Medical Center, Durham, NC, USA aut NATIONALLICENCE 700 1- Hauser Elizabeth Center for Human Genetics, Duke University Medical Center, 905 S. La Salle Street DUMC 3445, 27710, Durham, NC, USA aut NATIONALLICENCE 700 1- Gregory Simon Center for Human Genetics, Duke University Medical Center, 905 S. La Salle Street DUMC 3445, 27710, Durham, NC, USA aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 129/6(2011-06-01), 641-654 0340-6717 129:6<641 2011 129 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer