Journal article

Genetic profile of ischemic cerebrovascular disease and carotid stenosis

Kostulas K, Brophy V, Moraitis K, Manolescu A, Kostulas V, Gretarsdottir S, Cheng S, Hillert J ...see all

Acta Neurol Scand, vol. 118, issue 3 (2008) pp. 146-152

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Abstract

OBJECTIVES: Carotid artery stenosis (CS) is a major risk factor for ischemic cerebrovascular disease (ICVD) and is therefore of interest in genetic investigating. Here we report the distribution of 100 polymorphisms in 47 suspected susceptibility genes for ICVD and its risk factors. MATERIALS AND METHODS: Previously published markers in suspected susceptibility genes were genotyped in ICVD patients and controls (928/602). Genotyping was performed using multiplex polymerase chain reaction (PCR) and linear immobilized probe array assays. ICVD cases were subtyped according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) or subdivided into CS and non-CS patients by ultrasonography in a separate analysis. RESULTS: Three polymorphisms located in the lipoprotein lipase (LPL), angiotensinogen (AGT) and guanine nucleotide-binding protein beta-3 (GNB3) genes were significantly associated with ICVD after correction for age and gender. The strongest association was found for the protective LPL Ser447Term polymorphism. All the significant markers showed varying frequencies in different subphenotypes of ICVD. Factor VII, apolipoprotein E and two renin polymorphisms were differentially frequent in patients with evidence of CS compared with non-CS patients. CONCLUSIONS: We have found that some previously described susceptibility polymorphisms are weakly associated with ICVD and that subdivision of patients into CS and non-CS groups may help to identify new candidate polymorphisms.

Author-supplied keywords

  • *Genetic Predisposition to Disease
  • Angiotensinogen/*genetics
  • Biological Markers/analysis
  • Brain Ischemia/*genetics
  • Carotid Stenosis/*genetics
  • Female
  • Heterotrimeric GTP-Binding Proteins/*genetics
  • Humans
  • Lipoprotein Lipase/*genetics
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Genetic

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Authors

  • K Kostulas

  • V H Brophy

  • K Moraitis

  • A Manolescu

  • V Kostulas

  • S Gretarsdottir

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