title: Association of apolipoprotein E4 and haplotypes of the apolipoprotein E gene with lobar intracerebral hemorrhage.
abstract: OBJECTIVE
  Conflicting reports in the literature exist with regard to the association of apolipoprotein E (apo E) alleles and lobar intracerebral hemorrhage (ICH). We genotyped 12 single-nucleotide polymorphisms in the 5' upstream regulatory, exonic, and intronic regions of the apo E gene and performed genotype and haplotype association analyses.
  
  
  METHODS
  We prospectively enrolled subjects with hemorrhagic stroke and matched them with 2 controls based on age, race, and sex. Each case was reviewed by a physician to determine case status and location of the ICH. Multivariate logistic-regression modeling with backward elimination was used to determine significant risk factors for lobar ICH. Associations at the genotype and haplotype levels and linkage disequilibrium were conducted according to standard statistical methods.
  
  
  RESULTS
  Between May 1997 and December 2002, 315 cases of ICH were recruited, of whom 107 were lobar ICH cases matched to 205 controls. No association was found for apo E2, E3, or E4 with nonlobar ICH. Independent, significant risk factors for lobar ICH included apo E4, untreated hypertension, anticoagulant use, a first-degree relative with ICH, and < or =high school education (compared with >high school education). Treated hypercholesterolemia compared with "no history of hypercholesterolemia" was associated with a decreased risk of lobar ICH. Haplotype association analysis demonstrated a significant association of the apo E gene with lobar ICH among whites (P<0.0001) and blacks (P=0.0024).
  
  
  CONCLUSIONS
  Apo E4 is independently associated with lobar ICH but not nonlobar ICH. Haplotypes of the apo E gene are associated with lobar ICH. Untreated hypertension is a risk factor for lobar ICH.
authors.affiliation: University of Cincinnati, Cincinnati, OH, USA. daniel.woo@uc.edu
authors.forename: Daniel
authors.initials: D
authors.lastname: Woo
authors.forename: Ritesh
authors.initials: R
authors.lastname: Kaushal
authors.forename: Ranajit
authors.initials: R
authors.lastname: Chakraborty
authors.forename: Jessica
authors.initials: J
authors.lastname: Woo
authors.forename: Mary
authors.initials: M
authors.lastname: Haverbusch
authors.forename: Padmini
authors.initials: P
authors.lastname: Sekar
authors.forename: Brett
authors.initials: B
authors.lastname: Kissela
authors.forename: Arthur
authors.initials: A
authors.lastname: Pancioli
authors.forename: Edward
authors.initials: E
authors.lastname: Jauch
authors.forename: Dawn
authors.initials: D
authors.lastname: Kleindorfer
authors.forename: Matthew
authors.initials: M
authors.lastname: Flaherty
authors.forename: Alexander
authors.initials: A
authors.lastname: Schneider
authors.forename: Pooja
authors.initials: P
authors.lastname: Khatri
authors.forename: Laura
authors.initials: L
authors.lastname: Sauerbeck
authors.forename: Jane
authors.initials: J
authors.lastname: Khoury
authors.forename: Ranjan
authors.initials: R
authors.lastname: Deka
authors.forename: Joseph
authors.initials: J
authors.lastname: Broderick
mesh_terms: D000483:Alleles; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D044383:Black People; D016022:Case-Control Studies; D002543:Cerebral Hemorrhage / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006470:Hemorrhage; D006801:Humans; D006973:Hypertension / Q000235:genetics; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012306:Risk; D018570:Risk Assessment; D012307:Risk Factors; D044465:White People
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E