Published online before print January 12, 2006, doi: 10.1161/01.STR.0000200449.58684.8a
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(Stroke. 2006;37:288.)
© 2006 American Heart Association, Inc.
Advances in Stroke 2005 |
Update on Genetics of Stroke and Cerebrovascular Disease 2005
From the Clinical Neuroscience (H.S.M.), St Georges, University of London, London, UK; and the Department of Neurology (M.J.A.), Northwestern University, Feinberg School of Medicine, Chicago, IL.
Correspondence to Hugh S. Markus, Centre for Clinical Neuroscience, St Georges, University of London, Cranmer Terrace, London SW17 ORW. E-mail h.markus@sgul.ac.uk
Key Words: CADASIL • genetics • stroke
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Over the past 2 years this update reported the identification by the Icelandic Decode group of 2 novel genes associated with ischemic stroke: phosphodiesterase 4D gene (PDE4D) and 5-Lipoxygenase activating protein (ALOX5AP).1,2 These putative associations have been with specific haplotypes of each gene, but no disease-specific mutations in either gene have been identified.
PDE4D, a cyclic nucleotide phosphodiesterase, selectively degrades second messenger cAMP (cAMP). Reduced cAMP levels are associated with increased smooth muscle cell proliferation and migration, key events in atherosclerosis, making an association with stroke pathophysiologically plausible. Consistent with this, the initial association was reported only with large artery and cardioembolic stroke subtypes.2 Studies over the last year attempting to replicate this association have produced diverse results. In a UK population no overall association was found with ischemic stroke, but possible associations were identified with cardioembolic and large artery stroke.3 An American study reported an association with ischemic stroke, particularly large artery stroke.4 In contrast, no association was found in a German stroke cohort,5 or a Swedish stroke cohort aged <75 years.6 A linkage study from a second Swedish population confirmed linkage to 5q12,6 but no linkage study could be found in an American population.4 No association was found with carotid intima-media thickness,3 suggesting PDE4D does not exert its effects via accelerating early atherosclerosis.
ALOX5AP codes for 5-lipoxygenase activating protein which is essential for conversion of arachadonic acid to leukotriene A4, a process catabolized by 5-lipooxygenase. LTA4 is converted into LTB4, which plays
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