title: APOE and AGT in the Finnish p.Arg133Cys CADASIL population.
abstract: BACKGROUND
  CADASIL is an inherited systemic small vessel disease, the affected status of brain vessels leading to subcortical vascular dementia. The defective gene is NOTCH3 in which over 230 different pathogenic mutations have been identified. The clinical course of CADASIL is highly variable even within families. Previous studies have shown that additional genetic factors modify the phenotype.
  
  
  OBJECTIVE
  Altogether, 134 Finnish CADASIL patients with p.Arg133Cys mutation were analysed for possible associations between the apolipoprotein E (APOE) genotype, angiotensinogen (AGT) p.Met268Thr polymorphism or neutral p.Ala202Ala NOTCH3 polymorphism and earlier first-ever stroke or migraine.
  
  
  RESULTS
  We found no association between the APOE genotypes, AGT polymorphism, NOTCH3 polymorphism and earlier first-ever stroke or migraine.
  
  
  CONCLUSIONS
  The APOE, AGT and NOTCH3 polymorphism did not modify the onset of strokes or migraine in our CADASIL sample, which is one of the largest mutationally homogenous CADASIL populations published to date. International collaboration, pooled analyses and genomewide approaches are warranted to identify the genetic factors that modify the highly variable CADASIL phenotype.
authors.affiliation: Department of Medical Biochemistry and Genetics, Institute of Biomedicine, University of Turku, Turku, Finland.|Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Siitonen
authors.affiliation: Department of Medical Biochemistry and Genetics, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Mykkänen
authors.affiliation: Stroke Unit and Neurology, Azienda Ospedaliero Universitaria Careggi, Florence, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Pescini
authors.affiliation: Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Rovio
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Kääriäinen
authors.affiliation: Protein Chemistry Unit, Institute of Biomedicine/Anatomy, University of Helsinki, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Baumann
authors.affiliation: Department of Clinical Genetics, HUSLAB Helsinki University Central Hospital and Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Pöyhönen
authors.affiliation: Department of Geriatrics, Turku City Hospital and University of Turku, Turku, Finland.|Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Viitanen
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000808:Angiotensinogen / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D046589:CADASIL / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000209:etiology; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics; D020521:Stroke / Q000453:epidemiology; D055815:Young Adult
chemical_list: C534931:AGT protein, human; D001057:Apolipoproteins E; C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D000808:Angiotensinogen
keywords: AGT; APOE; CADASIL; NOTCH3; association study; founder effect; genotype-phenotype correlation