title: Assessment of the genetic effects of polymorphisms in the osteoprotegerin gene, TNFRSF11B, on serum osteoprotegerin levels and carotid plaque vulnerability.
abstract: OBJECTIVE
  Osteoprotegerin (OPG) is a secretory glycoprotein which belongs to the tumor necrosis factor receptor family. Various mechanisms have been suggested by which calcification might alter atherosclerotic plaque stability, but the significance of this intimal calcification is controversial. High concentrations of OPG have been associated with the presence of vascular and cardiovascular diseases. This study was designed to assess the association between gene polymorphisms of the OPG gene (TNFRSF11B), the serum OPG level, and plaque stability in patients with carotid atherosclerosis.
  
  
  METHODS
  We studied 177 patients with internal carotid artery stenosis who underwent carotid endarterectomy and also 303 controls. Carotid endarterectomy samples removed from patients were assessed by immunohistochemistry. Concentrations of OPG were measured and gene polymorphisms were examined by polymerase chain reaction and restriction enzyme analysis and were compared, initially between patients with carotid atherosclerosis and controls, and subsequently between stable and unstable carotid plaques.
  
  
  RESULTS
  We found that the GG genotype of the T245G polymorphism, the CC genotype of the T950C polymorphism, and the CC genotype of the G1181C polymorphism were significantly higher in patients with carotid plaque than in controls (21.5% versus 10.9% , P<0.01; 15.8% versus 7.6%, P<0.01; and 20.3% versus 10.9%, P<0.01, respectively) and that these polymorphisms were associated with high serum OPG levels (4.02 [3.07] versus 2.94 [1.81] pmol/L; P<0.01), which were significantly higher in patients with unstable atherosclerotic plaques (5.86 [4.02] versus 3.53 [1.87] pmol/L; P<0.01).
  
  
  CONCLUSIONS
  The TNFRSF11B gene polymorphisms studied are associated with high serum OPG levels and might be potential markers for plaque instability.
authors: Vascular Medicine and Atherothrombosis Laboratory, Department of Experimental Medicine, Sapienza University of Rome, Polo Pontino, Italy.
authors: Giuseppe
authors: G
authors: Straface
authors: Federico
authors: F
authors: Biscetti
authors: Dario
authors: D
authors: Pitocco
authors: Giovanni
authors: G
authors: Bertoletti
authors: Maria
authors: M
authors: Misuraca
authors: Claudio
authors: C
authors: Vincenzoni
authors: Francesco
authors: F
authors: Snider
authors: Vincenzo
authors: V
authors: Arena
authors: Egidio
authors: E
authors: Stigliano
authors: Flavia
authors: F
authors: Angelini
authors: Luigi
authors: L
authors: Iuliano
authors: Stefania
authors: S
authors: Boccia
authors: Chiara
authors: C
authors: de Waure
authors: Francesco
authors: F
authors: Giacchi
authors: Giovanni
authors: G
authors: Ghirlanda
authors: Andrea
authors: A
authors: Flex
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016893:Carotid Stenosis / Q000097:blood* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood* / Q000235:genetics*; D058226:Plaque, Atherosclerotic / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D015415:Biomarkers; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human