TY - JOUR
T1 - Association of Phosphodiesterase 4D with ischemic stroke
T2 - A population-based case-control study
AU - Woo, Daniel
AU - Kaushal, Ritesh
AU - Kissela, Brett
AU - Sekar, Padmini
AU - Wolujewicz, Michael
AU - Pal, Prodipto
AU - Alwell, Kathleen
AU - Haverbusch, Mary
AU - Ewing, Irene
AU - Miller, Rosie
AU - Kleindorfer, Dawn
AU - Flaherty, Matthew
AU - Chakraborty, Ranajit
AU - Deka, Ranjan
AU - Broderick, Joseph
PY - 2006/2
Y1 - 2006/2
N2 - Background and Purpose - The Phosphodiesterase 4D (PDE4D) gene was reported recently to be associated with ischemic stroke in an Icelandic population. The association was found predominately with large vessel and cardioembolic stroke. However, 2 recent reports were unable to confirm this association, although a trend toward association with cardioembolic stroke was reported. None of the reports included significant proportions of blacks. We tested for genotype and haplotype association of polymorphisms of the PDE4D gene with ischemic stroke in a population-based, biracial, case-control study. Methods - A total of 357 cases of ischemic stroke and 482 stroke-free controls from the same community were examined. Single nucleotide polymorphisms (SNPs) were chosen based on significant associations reported previously. Linkage disequilibrium (LD), SNP, and haplotype association analysis was performed using PHASE 2.0 and Haploview 3.2. Results - Although several univariate associations were identified, only 1 SNP (rs2910829) was found to be significantly associated with cardioembolic stroke among both whites and blacks. The rs152312 SNP was associated with cardioembolic stroke among whites after multiple comparison corrections. The same SNP was not associated with cardioembolic stroke among blacks. However, significant haplotype association was identified for both whites and blacks for all ischemic stroke, cardioembolic stroke, and stroke of unknown origin. Haplotype association was identified for small vessel stroke among whites. Conclusions - PDE4D is a risk factor for ischemic stroke and, in particular, for cardioembolic stroke, among whites and blacks. Further study of this gene is warranted.
AB - Background and Purpose - The Phosphodiesterase 4D (PDE4D) gene was reported recently to be associated with ischemic stroke in an Icelandic population. The association was found predominately with large vessel and cardioembolic stroke. However, 2 recent reports were unable to confirm this association, although a trend toward association with cardioembolic stroke was reported. None of the reports included significant proportions of blacks. We tested for genotype and haplotype association of polymorphisms of the PDE4D gene with ischemic stroke in a population-based, biracial, case-control study. Methods - A total of 357 cases of ischemic stroke and 482 stroke-free controls from the same community were examined. Single nucleotide polymorphisms (SNPs) were chosen based on significant associations reported previously. Linkage disequilibrium (LD), SNP, and haplotype association analysis was performed using PHASE 2.0 and Haploview 3.2. Results - Although several univariate associations were identified, only 1 SNP (rs2910829) was found to be significantly associated with cardioembolic stroke among both whites and blacks. The rs152312 SNP was associated with cardioembolic stroke among whites after multiple comparison corrections. The same SNP was not associated with cardioembolic stroke among blacks. However, significant haplotype association was identified for both whites and blacks for all ischemic stroke, cardioembolic stroke, and stroke of unknown origin. Haplotype association was identified for small vessel stroke among whites. Conclusions - PDE4D is a risk factor for ischemic stroke and, in particular, for cardioembolic stroke, among whites and blacks. Further study of this gene is warranted.
KW - Epidemiology
KW - Genetics
KW - Ischemic
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=33644860685&partnerID=8YFLogxK
U2 - 10.1161/01.STR.0000198843.72824.0a
DO - 10.1161/01.STR.0000198843.72824.0a
M3 - Article
C2 - 16373644
AN - SCOPUS:33644860685
SN - 0039-2499
VL - 37
SP - 371
EP - 376
JO - Stroke
JF - Stroke
IS - 2
ER -