Published Online
on December 22, 2005

A more recent version of this article appeared on February 1, 2006

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Submitted on October 6, 2005
Revised on October 21, 2005
Accepted on October 28, 2005

Association of Phosphodiesterase 4D With Ischemic Stroke. A Population-Based Case-Control Study

Daniel Woo MD, MS^*; Ritesh Kaushal MD; Brett Kissela MD; Padmini Sekar MS; Michael Wolujewicz MS; Prodipto Pal MD; Kathleen Alwell RN; Mary Haverbusch RN; Irene Ewing RN; Rosie Miller RN; Dawn Kleindorfer MD; Matthew Flaherty MD; Ranajit Chakraborty PhD; Ranjan Deka PhD; and Joseph Broderick MD

From the Department of Neurology, University of Cincinnati College of Medicine, Ohio.

^* To whom correspondence should be addressed. E-mail: Daniel.woo{at}uc.edu.

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.

Key words: epidemiology • genetics • stroke, ischemic

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