Genetic factor in stroke susceptibility

16 May 2005

Stroke is the most common cause of severe disability and the third most common cause of death in the UK, accounting for over 8% of all deaths in men and 13% of all deaths in women. It therefore represents a major health burden. Ischemic stroke, caused by blockage of a cerebral artery, is the predominant form of the disease. Besides known environmental factors such as hypertension, atherosclerosis, smoking and diabetes that may predispose an individual to suffering a stroke, the disease also has a genetic component; family history of stroke is known to be an independent risk factor for developing the disease.

In the October edition of Nature Genetics, an association between the gene encoding phosphodiesterase 4D (PDE4D) and ischemic stroke is reported [Gretarsdottir, S. et al. (2003) Nature Genetics 35, 131-138]. PDE4D is a complex gene with multiple different isoforms (functional variants with different N-terminal regulatory domains). Gretarsdottir and colleagues found that relative expression patterns of the PDE4D isoforms correlated with the incidence of stroke. They report a disease-associated haplotype (set of closely linked genetic markers) for the PDE4D gene, carried as a single copy by around 16% of the general population and present as a double copy in less than 1%. The paper reports that the PDE4D gene is most strongly associated with forms of stroke related to atherosclerosis, and propose that the PDE4D enzyme is involved in the pathogenesis of stroke, suggesting that inhibition of PDE4D could reduce the risk of stroke in individuals with a genetic predisposition towards the disease.

Comment: This is the first reported association between a specific gene and the risk of stroke, which now joins a small group of multifactorial diseases (including diabetes and Alzheimer

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