TY - JOUR
T1 - Association of apolipoprotein E4 and haplotypes of the apolipoprotein E gene with lobar intracerebral hemorrhage
AU - Woo, Daniel
AU - Kaushal, Ritesh
AU - Chakraborty, Ranajit
AU - Woo, Jessica
AU - Haverbusch, Mary
AU - Sekar, Padmini
AU - Kissela, Brett
AU - Pancioli, Arthur
AU - Jauch, Edward
AU - Kleindorfer, Dawn
AU - Flaherty, Matthew
AU - Schneider, Alexander
AU - Khatri, Pooja
AU - Sauerbeck, Laura
AU - Khoury, Jane
AU - Deka, Ranjan
AU - Broderick, Joseph
PY - 2005/9
Y1 - 2005/9
N2 - Background and Purpose - 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 ≤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.
AB - Background and Purpose - 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 ≤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.
KW - Apolipoproteins
KW - Epidemiology
KW - Genetics
KW - Intracerebral hemorrhage
UR - http://www.scopus.com/inward/record.url?scp=24644518521&partnerID=8YFLogxK
U2 - 10.1161/01.STR.0000177891.15082.b9
DO - 10.1161/01.STR.0000177891.15082.b9
M3 - Review article
C2 - 16100021
AN - SCOPUS:24644518521
SN - 0039-2499
VL - 36
SP - 1874
EP - 1879
JO - Stroke
JF - Stroke
IS - 9
ER -