Association of apolipoprotein E4 and haplotypes of the apolipoprotein E gene with lobar intracerebral hemorrhage.
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.
Woo
Daniel
D
University of Cincinnati, Cincinnati, OH, USA. daniel.woo@uc.edu
Kaushal
Ritesh
R
Chakraborty
Ranajit
R
Woo
Jessica
J
Haverbusch
Mary
M
Sekar
Padmini
P
Kissela
Brett
B
Pancioli
Arthur
A
Jauch
Edward
E
Kleindorfer
Dawn
D
Flaherty
Matthew
M
Schneider
Alexander
A
Khatri
Pooja
P
Sauerbeck
Laura
L
Khoury
Jane
J
Deka
Ranjan
R
Broderick
Joseph
J
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
D053327:Apolipoprotein E4; D001057:Apolipoproteins E