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(Stroke. 2006;37:1955.)
© 2006 American Heart Association, Inc.

Editorials

PDE4D and Stroke

A Real Advance or a Case of the Emperor’s New Clothes?

Bradford B. Worrall, MD, MSc Josyf C. Mychaleckyj, MA, DPhil

From the University of Virginia Health System (B.B.W.), Departments of Neurology and Public Health Sciences, Charlottesville, Va; and the Center for Human Genomics (J.C.M.), Wake Forest University School of Medicine, Winston-Salem, NC.

Correspondence to Bradford B. Worrall, MD, MSc, University of Virginia Health System, Department of Neurology, Box 800394, Charlottesville, VA 22908. E-mail bbw9r@virginia.edu

Key Words: genetics • hypertension • phosphodiesterase • polymorphism, genetic • stroke

An extract of the first 250 words of the full text is provided, because this article has no abstract.

See related article, pages 2012–2017.

In Hans Christian Andersen’s beloved tale,¹ it is the innocent child who finally reveals what others had been unable to admit. Deference to the King’s court and perceived wisdom discomforts other subjects in the kingdom from questioning the sovereign’s taste in garments. Since the original article identifying PDE4D as the putative stroke 1 (STRK1) locus,² many groups from around the globe have attempted to validate the association. Stroke is a syndrome not a disease, with numerous interrelated phenotypes and subphenotypes. The challenges of sorting out the genetic contributions to complex diseases such as stroke are substantial, but the potential rewards in the forms of new treatments and improved understanding of pathophysiology are great. In the face of the great promise of the PDE4D tale, we need to assess the state of our knowledge clearly and honestly.

Before the report by deCODE Genetics, the PDE4 family of genes had not been tested as candidate genes for any disease or phenotype, although the biochemical role of PDE4D as a regulator of cAMP signal transduction was recognized. The PDE4D gene product (cAMP specific 3',5'-cyclic phosphodiesterase 4D) appears to be a secondary signal pathway regulator of phenotype, with indirect effects on cardiovascular or stroke biomarkers.³ Nonetheless, because PDE4 enzymes predominate cAMP metabolism in inflammatory cells, and PDE4D accounts for at least 80% of PDE activity in inflammatory cells,^4,5 the PDE4D is a plausible candidate gene. PDE4D enzyme activity could play an important role in stroke risk . . . [Full Text of this Article]

Related Article:

Polymorphisms of the Phosphodiesterase 4D, cAMP-Specific (PDE4D) Gene and Risk of Ischemic Stroke: A Prospective, Nested Case–Control Evaluation

Robert Y.L. Zee, Victoria H. Brophy, Suzanne Cheng, Hillary H Hegener, Henry A. Erlich, and Paul M Ridker
Stroke 2006 37: 2012-2017. [Abstract] [Full Text] [PDF]

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