Human Genetics

, Volume 129, Issue 6, pp 641–654

Polymorphic variants in tenascin-C (TNC) are associated with atherosclerosis and coronary artery disease

Authors

  • Mollie A. Minear
    • Center for Human GeneticsDuke University Medical Center
  • David R. Crosslin
    • Department of BiostatisticsUniversity of Washington
  • Beth S. Sutton
    • School of PharmacyCampbell University
  • Jessica J. Connelly
    • Robert M. Berne Cardiovascular Research CenterUniversity of Virginia
  • Sarah C. Nelson
    • Department of BiostatisticsUniversity of Washington
  • Shera Gadson-Watson
    • Center for Human GeneticsDuke University Medical Center
  • Tianyuan Wang
    • Institute for Genome Sciences and PolicyDuke University
  • David Seo
    • Miller School of MedicineUniversity of Miami
  • Jeffrey M. Vance
    • Miller School of MedicineUniversity of Miami
  • Michael H. SketchJr.
    • Department of MedicineDuke University Medical Center
  • Carol Haynes
    • Center for Human GeneticsDuke University Medical Center
  • Pascal J. Goldschmidt-Clermont
    • Miller School of MedicineUniversity of Miami
  • Svati H. Shah
    • Center for Human GeneticsDuke University Medical Center
    • Department of MedicineDuke University Medical Center
  • William E. Kraus
    • Department of MedicineDuke University Medical Center
  • Elizabeth R. Hauser
    • Center for Human GeneticsDuke University Medical Center
    • Department of MedicineDuke University Medical Center
    • Center for Human GeneticsDuke University Medical Center
    • Department of MedicineDuke University Medical Center
Original Investigation

DOI: 10.1007/s00439-011-0959-z

Cite this article as:
Minear, M.A., Crosslin, D.R., Sutton, B.S. et al. Hum Genet (2011) 129: 641. doi:10.1007/s00439-011-0959-z

Abstract

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.

Copyright information

© Springer-Verlag 2011