title: LDL receptor mutations and ApoB mutations are not risk factors for ischemic cerebrovascular disease of the young, but lipids and lipoproteins are.
abstract: BACKGROUND
  The genetic background for ischemic cerebrovascular disease of the young and the role of lipids and lipoproteins as risk factors are not clear.
  
  
  METHODS
  We determined five LDL receptor mutations (Trp23Stop, Trp66Gly, Trp556Ser, 313+1G --> A, 1846-1G --> A) and three apolipoprotein B mutations (Arg3500Gln, Arg3500Trp, Arg3531Cys), and other risk factors for ischemic cerebrovascular disease in 80 patients (36 women, 44 men) with onset of disease before the age of 50 years compared with 3366 individuals from a general population sample within the same age range.
  
  
  RESULTS
  None of the patients were carriers of mutations in the LDL receptor (Trp23Stop, Trp66Gly, Trp556Ser, 313+1G --> A, 1846 - 1G --> A) or the apolipoprotein B gene (Arg3500Gln, Arg3500Trp, Arg3531Cys) associated with hypercholesterolemia. However, on univariate analysis as well as on logistic regression analysis allowing for age and gender, plasma cholesterol (OR 1.4; P < 0.0005), HDL-cholesterol (OR 0.4; P < 0.005), diabetes (OR 5.8; P < 0.0001), and hypertension (OR 3.9; P < 0.001) were significant predictors of ischemic cerebrovascular disease.
  
  
  CONCLUSIONS
  The five most common LDL receptor mutations in Danish patients with familial hypercholesterolemia and three mutations in the apolipoprotein B gene did not predispose to ischemic cerebrovascular disease of the young. However, cholesterol and HDL-cholesterol are important risk factors for ischemic cerebrovascular disease of the young in the present study. The elevation in cholesterol could in some patients be due to rare LDL receptor mutations not tested for, and could in other patients be multifactorial in origin.
authors.affiliation: Department of Neurology, Rigshospitalet, National University Hospital, Rigshospitalet, Denmark. ruth.frikke@image.dk
authors.forename: R
authors.initials: R
authors.lastname: Frikke-Schmidt
authors.forename: P
authors.initials: P
authors.lastname: Arlien-Søborg
authors.forename: S
authors.initials: S
authors.lastname: Thorsen
authors.forename: H K
authors.initials: HK
authors.lastname: Jensen
authors.forename: S
authors.initials: S
authors.lastname: Vorstrup
mesh_terms: D000328:Adult; D000367:Age Factors; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics*; D002545:Brain Ischemia / Q000209:etiology / Q000235:genetics*; D002536:Cerebral Arteries / Q000473:pathology / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000209:etiology* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood / Q000235:genetics*; D008074:Lipoproteins / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011973:Receptors, LDL / Q000097:blood / Q000235:genetics*; D012307:Risk Factors
chemical_list: D001055:Apolipoproteins B; D008055:Lipids; D008074:Lipoproteins; D011973:Receptors, LDL