Association of Phosphodiesterase 4D with ischemic stroke: a population-based case-control study.
OBJECTIVE
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.
Woo
Daniel
D
Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0525, USA. Daniel.woo@uc.edu
Kaushal
Ritesh
R
Kissela
Brett
B
Sekar
Padmini
P
Wolujewicz
Michael
M
Pal
Prodipto
P
Alwell
Kathleen
K
Haverbusch
Mary
M
Ewing
Irene
I
Miller
Rosie
R
Kleindorfer
Dawn
D
Flaherty
Matthew
M
Chakraborty
Ranajit
R
Deka
Ranjan
R
Broderick
Joseph
J
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics* / Q000502:physiology*; D000367:Age Factors; D000368:Aged; D044383:Black People; D016022:Case-Control Studies; D015331:Cohort Studies; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004247:DNA / Q000737:chemistry; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007511:Ischemia / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000235:genetics; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011786:Quality Control; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D044465:White People
D004247:DNA; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517376:PDE4D protein, human