title: Proprotein convertase subtilisin/kexin type 9 (PCSK9) gene is a risk factor of large-vessel atherosclerosis stroke.
abstract: OBJECTIVE
  Genetic variation in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene has been recently identified as an important determinant of plasma LDL-cholesterol and severity of coronary heart disease. We studied whether the PCSK9 gene is linked to the risk of ischemic stroke (IS) and with the development of intracranial atherosclerosis.
  
  
  RESULTS
  The pivotal E670G polymorphism, tagging an important haplotype of the PCSK9 gene, was genotyped in two independent studies. The Belgium Stroke Study included 237 middle aged (45-60) Belgian patients, with small-vessel occlusion (SVO) and large-vessel atherosclerosis stroke (LVA), and 326 gender and ethnicity matched controls (>60 yrs) without a history of stroke. In multivariate analysis the minor allele (G) carriers appeared as a significant predictor of LVA (OR = 3.52, 95% CI 1.25-9.85; p = 0.017). In a Finnish crossectional population based consecutive autopsy series of 604 males and females (mean age 62.5 years), G-allele carriers tended to have more severe allele copy number-dependent (p = 0.095) atherosclerosis in the circle of Willis and in its branches.
  
  
  CONCLUSIONS
  Our findings in this unique combination of clinical and autopsy data, provide evidence that PCSK9 gene associates with the risk of LVA stroke subtype, and suggest that the risk is mediated by the severity of intracranial atherosclerosis.
authors.affiliation: Laboratory of Experimental Neurology, Department of Neurology, Erasme Hospital, Universite Libre de Bruxelles, Brussels, Belgium. shabboud@ulb.ac.be
authors.forename: Shérine
authors.initials: S
authors.lastname: Abboud
authors.forename: Pekka J
authors.initials: PJ
authors.lastname: Karhunen
authors.forename: Dieter
authors.initials: D
authors.lastname: Lütjohann
authors.forename: Sirkka
authors.initials: S
authors.lastname: Goebeler
authors.forename: Teemu
authors.initials: T
authors.lastname: Luoto
authors.forename: Silvia
authors.initials: S
authors.lastname: Friedrichs
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimaki
authors.forename: Massimo
authors.initials: M
authors.lastname: Pandolfo
authors.forename: Reijo
authors.initials: R
authors.lastname: Laaksonen
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000235:genetics*; D016022:Case-Control Studies; D002536:Cerebral Arteries / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012306:Risk; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics* / Q000502:physiology*; D020521:Stroke / Q000235:genetics*
chemical_list: C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases