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Human Genetics

, Volume 129, Issue 6, pp 641–654 | Cite as

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

  • Mollie A. Minear
  • David R. Crosslin
  • Beth S. Sutton
  • Jessica J. Connelly
  • Sarah C. Nelson
  • Shera Gadson-Watson
  • Tianyuan Wang
  • David Seo
  • Jeffrey M. Vance
  • Michael H. SketchJr.
  • Carol Haynes
  • Pascal J. Goldschmidt-Clermont
  • Svati H. Shah
  • William E. Kraus
  • Elizabeth R. Hauser
  • Simon G. Gregory
Original Investigation

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.

Keywords

Coronary Artery Disease Cilostazol Aorta Sample Atherosclerotic Plaque Development Major Epicardial Vessel 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We would like to thank the subjects in the CATHGEN and GENECARD studies for their participation. We would also like to acknowledge the essential contributions of the following individuals for making this publication possible: Elaine Dowdy; the GENECARD Investigators Network; the CATHGEN Steering Committee Members; Charlotte Nelson, Paul Hofmann, and Judy Stafford at the Duke Clinical Research Institute; and the staff at the Duke University Center for Human Genetics. This work was supported by NIH grants HL073389 (Hauser) and HL73042 (Goldschmidt-Clermont, Kraus).

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Mollie A. Minear
    • 1
  • David R. Crosslin
    • 4
  • Beth S. Sutton
    • 5
  • Jessica J. Connelly
    • 6
  • Sarah C. Nelson
    • 4
  • Shera Gadson-Watson
    • 1
  • Tianyuan Wang
    • 3
  • David Seo
    • 7
  • Jeffrey M. Vance
    • 7
  • Michael H. SketchJr.
    • 2
  • Carol Haynes
    • 1
  • Pascal J. Goldschmidt-Clermont
    • 7
  • Svati H. Shah
    • 1
    • 2
  • William E. Kraus
    • 2
  • Elizabeth R. Hauser
    • 1
    • 2
  • Simon G. Gregory
    • 1
    • 2
  1. 1.Center for Human GeneticsDuke University Medical CenterDurhamUSA
  2. 2.Department of MedicineDuke University Medical CenterDurhamUSA
  3. 3.Institute for Genome Sciences and PolicyDuke UniversityDurhamUSA
  4. 4.Department of BiostatisticsUniversity of WashingtonSeattleUSA
  5. 5.School of PharmacyCampbell UniversityMorrisvilleUSA
  6. 6.Robert M. Berne Cardiovascular Research CenterUniversity of VirginiaCharlottesvilleUSA
  7. 7.Miller School of MedicineUniversity of MiamiMiamiUSA

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