The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Default user image.

Gustav Smith

Associate professor

Default user image.

Effects of the coronary artery disease associated LPA and 9p21 loci on risk of aortic valve stenosis

Author

  • Teresa Trenkwalder
  • Christopher P. Nelson
  • Muntaser D. Musameh
  • Ify R. Mordi
  • Thorsten Kessler
  • Costanza Pellegrini
  • Radoslaw Debiec
  • Tobias Rheude
  • Viktor Lazovic
  • Lingyao Zeng
  • Andreas Martinsson
  • J. Gustav Smith
  • Jesper R. Gådin
  • Anders Franco-Cereceda
  • Per Eriksson
  • Jonas B. Nielsen
  • Sarah E. Graham
  • Cristen J. Willer
  • Kristian Hveem
  • Adnan Kastrati
  • Peter S. Braund
  • Colin N.A. Palmer
  • Amparo Aracil
  • Oliver Husser
  • Wolfgang Koenig
  • Heribert Schunkert
  • Chim C. Lang
  • Christian Hengstenberg
  • Nilesh J. Samani

Summary, in English

Background: Aortic valve stenosis (AVS) and coronary artery disease (CAD) have a significant genetic contribution and commonly co-exist. To compare and contrast genetic determinants of the two diseases, we investigated associations of the LPA and 9p21 loci, i.e. the two strongest CAD risk loci, with risk of AVS. Methods: We genotyped the CAD-associated variants at the LPA (rs10455872) and 9p21 loci (rs1333049) in the GeneCAST (Genetics of Calcific Aortic STenosis) Consortium and conducted a meta-analysis for their association with AVS. Cases and controls were stratified by CAD status. External validation of findings was undertaken in five cohorts including 7880 cases and 851,152 controls. Results: In the meta-analysis including 4651 cases and 8231 controls the CAD-associated allele at the LPA locus was associated with increased risk of AVS (OR 1.37; 95%CI 1.24–1.52, p = 6.9 × 10−10) with a larger effect size in those without CAD (OR 1.53; 95%CI 1.31–1.79) compared to those with CAD (OR 1.27; 95%CI 1.12–1.45). The CAD-associated allele at 9p21 was associated with a trend towards lower risk of AVS (OR 0.93; 95%CI 0.88–0.99, p = 0.014). External validation confirmed the association of the LPA risk allele with risk of AVS (OR 1.37; 95%CI 1.27–1.47), again with a higher effect size in those without CAD. The small protective effect of the 9p21 CAD risk allele could not be replicated (OR 0.98; 95%CI 0.95–1.02). Conclusions: Our study confirms the association of the LPA locus with risk of AVS, with a higher effect in those without concomitant CAD. Overall, 9p21 was not associated with AVS.

Department/s

  • Cardiovascular Epigenetics
  • EpiHealth: Epidemiology for Health
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2019-02

Language

English

Pages

212-217

Publication/Series

International Journal of Cardiology

Volume

276

Document type

Journal article

Publisher

Elsevier

Topic

  • Cardiac and Cardiovascular Systems
  • Medical Genetics

Keywords

  • 9p21
  • Aortic valve stenosis
  • Lipoprotein (a)
  • Risk factors
  • Valvular heart disease

Status

Published

Research group

  • Cardiovascular Epigenetics

ISBN/ISSN/Other

  • ISSN: 0167-5273