title: Identification of a potential proinflammatory genetic profile influencing carotid plaque vulnerability.
abstract: OBJECTIVE
  Atherosclerosis and vascular remodeling after injury are driven by inflammation and mononuclear cell infiltration. Unstable atherosclerotic plaques are characterized by a large necrotic core. In this study we investigated the distribution and interaction between gene polymorphisms encoding proinflammatory molecules in an Italian population with internal carotid artery stenosis (ICAS). We also evaluated whether reciprocal interaction between these gene polymorphisms increased the risk of plaque vulnerability.
  
  
  METHODS
  In this genetic association study, 11 proinflammatory gene polymorphisms were analyzed in 933 individuals comprising 344 patients with ICAS who underwent carotid endarterectomy and 589 controls without ultrasound evidence of atherosclerosis or intimal thickening.
  
  
  RESULTS
  We found that interleukin (IL) 6 (IL-6), IL-1β, monocyte chemoattractant protein-1 (CCL2) macrophage inflammatory protein-1α (CCL3), E-selectin (SELE), intercellular adhesion molecule 1 (ICAM1), and matrix metalloproteinase-3 (MMP-3), and 9 (MMP-9) gene variants were independently and significantly associated with ICAS. The association remained significant even after the Bonferroni correction. We also found a genetic profile associated with different risks for ICAS, depending on the number of high-risk genotypes simultaneously present in an individual. Furthermore, proinflammatory genetic profiles are significantly more common in individuals with unstable carotid plaque.
  
  
  CONCLUSIONS
  Our study shows, for the first time, a reciprocal interaction between proinflammatory genotypes for the development and progression of ICAS.
authors.affiliation: Department of Medicine, A. Gemelli University Hospital, Catholic University School of Medicine, Rome, Italy; Laboratory of Vascular Biology and Genetics, Catholic University School of Medicine, Rome, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Biscetti
authors.affiliation: Department of Medicine, St M. Goretti Hospital, Latina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Straface
authors.affiliation: Department of Vascular Surgery, St M. Goretti Hospital, Latina, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bertoletti
authors.affiliation: Department of Vascular Surgery, A. Gemelli University Hospital, Catholic University School of Medicine, Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Vincenzoni
authors.affiliation: Department of Vascular Surgery, A. Gemelli University Hospital, Catholic University School of Medicine, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Snider
authors.affiliation: Department of Pathology, Catholic University School of Medicine, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Arena
authors.affiliation: Department of Medicine, A. Gemelli University Hospital, Catholic University School of Medicine, Rome, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Landolfi
authors.affiliation: Department of Medicine, A. Gemelli University Hospital, Catholic University School of Medicine, Rome, Italy; Laboratory of Vascular Biology and Genetics, Catholic University School of Medicine, Rome, Italy. Electronic address: andrea.flex@rm.unicatt.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Flex
mesh_terms: D000368:Aged; D002343:Carotid Artery, Internal / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery; D059168:Carotid Intima-Media Thickness; D016893:Carotid Stenosis / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000601:surgery; D016022:Case-Control Studies; D018450:Disease Progression; D016894:Endarterectomy, Carotid; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging / Q000235:genetics* / Q000276:immunology; D018836:Inflammation Mediators; D007558:Italy; D008297:Male; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012307:Risk Factors; D012422:Rupture, Spontaneous
chemical_list: D005819:Genetic Markers; D018836:Inflammation Mediators