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Phosphodiesterase 4D gene, ischemic stroke, and asymptomatic carotid atherosclerosis

S Bevan1, L Porteous, M Sitzer

  • 1Department of Clinical Neuroscience, St. George's Hospital Medical School, Tooting, London, UK. sbevan@sghms.ac.uk

Stroke
|April 2, 2005
PubMed

Insights

The Phosphodiesterase 4D (PDE4D) gene is not a significant risk factor for ischemic stroke or early atherosclerosis in European populations. A potential link to cardioembolic stroke exists, but not through accelerated atherosclerosis.

Area of Science:

  • Genetics and Genomics
  • Neurology
  • Cardiovascular Research

Background:

  • Phosphodiesterase 4D (PDE4D) was previously identified as a novel stroke gene linked to ischemic stroke, particularly large vessel and cardioembolic types.
  • This association suggested a potential role in accelerated atherosclerosis.
  • Replication in a non-Icelandic European population and assessment of early atherosclerosis were warranted.

Purpose of the Study:

  • To replicate the association of PDE4D with ischemic stroke in a European cohort.
  • To investigate PDE4D's role in specific stroke subtypes (large vessel, cardioembolic).
  • To assess PDE4D's association with asymptomatic atherosclerosis using carotid ultrasound.

Main Methods:

  • Case-control study involving 737 stroke patients and 933 controls.
  • Carotid intima-media thickness (IMT) and plaque assessed via ultrasound in 1000 community subjects.
  • Genotyping of 19 single nucleotide polymorphisms (SNPs) and 1 minisatellite in the PDE4D gene.

Main Results:

  • No overall association found between PDE4D and ischemic stroke.
  • Six SNPs associated with cardioembolic stroke; two different SNPs associated with large vessel disease.
  • No association observed between PDE4D and carotid artery IMT or plaque in asymptomatic individuals.

Conclusions:

  • PDE4D is not a major risk factor for ischemic stroke or early atherosclerosis in the studied European populations.
  • A possible association exists between PDE4D and cardioembolic stroke.
  • The lack of association with carotid atherosclerosis suggests alternative mechanisms for any PDE4D-related cardioembolic stroke risk.
Abstract

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