PLoS ONE (Jan 2012)

Genome-wide association study in a Lebanese cohort confirms PHACTR1 as a major determinant of coronary artery stenosis.

  • Jörg Hager,
  • Yoichiro Kamatani,
  • Jean-Baptiste Cazier,
  • Sonia Youhanna,
  • Michella Ghassibe-Sabbagh,
  • Daniel E Platt,
  • Antoine B Abchee,
  • Jihane Romanos,
  • Georges Khazen,
  • Raed Othman,
  • Danielle A Badro,
  • Marc Haber,
  • Angelique K Salloum,
  • Bouchra Douaihy,
  • Nabil Shasha,
  • Samer Kabbani,
  • Hana Sbeite,
  • Elie Chammas,
  • Hamid el Bayeh,
  • Francis Rousseau,
  • Diana Zelenika,
  • Ivo Gut,
  • Mark Lathrop,
  • Martin Farrall,
  • Dominique Gauguier,
  • Pierre A Zalloua,
  • FGENTCARD Consortium

DOI
https://doi.org/10.1371/journal.pone.0038663
Journal volume & issue
Vol. 7, no. 6
p. e38663

Abstract

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The manifestation of coronary artery disease (CAD) follows a well-choreographed series of events that includes damage of arterial endothelial cells and deposition of lipids in the sub-endothelial layers. Genome-wide association studies (GWAS) of multiple populations with distinctive genetic and lifestyle backgrounds are a crucial step in understanding global CAD pathophysiology. In this study, we report a GWAS on the genetic basis of arterial stenosis as measured by cardiac catheterization in a Lebanese population. The locus of the phosphatase and actin regulator 1 gene (PHACTR1) showed association with coronary stenosis in a discovery experiment with genome wide data in 1,949 individuals (rs9349379, OR = 1.37, p = 1.57×10(-5)). The association was replicated in an additional 2,547 individuals (OR = 1.31, p = 8.85×10(-6)), leading to genome-wide significant association in a combined analysis (OR = 1.34, p = 8.02×10(-10)). Results from this GWAS support a central role of PHACTR1 in CAD susceptibility irrespective of lifestyle and ethnic divergences. This association provides a plausible component for understanding molecular mechanisms involved in the formation of stenosis in cardiac vessels and a potential drug target against CAD.