Etiology and pathophysiology of stroke as a complex trait

Stroke (brain attack) is currently the third leading cause of death in West ern societies. Recent advances in molecular genetics have finally demonstra ted what has long been suggested by the clinical observation, that is, stro ke is not only the complication of major pathologic conditions such as athe rosclerosis, hypertension, or cardiac diseases, but rather it represents a complex trait itself. Thus, the pathogenesis of stroke is often the result of the combined effects of genes exerting a direct contributory role and of their interactions with several environmental determinants. A genetic dissection of stroke has been attempted in suitable animal models and in humans. With this approach, the genetic defects underlying monogeni c disorders associated with stroke were identified. Moreover, important fin dings have recently highlighted the contribution of genes encoding cardiova scular hormones, such as the atrial natriuretic peptide, for the pathogenes is of multifactorial, polygenic forms of stroke. A more thorough understanding of the fine mechanisms, dependent from mutati ons within stroke susceptibility genes and underlying the disease pathogene sis, may help to introduce new specific tools to achieve better prevention and treatment of stroke. Am J Hypertens 2000; 13:1139-1148 (C) 2000 America n Journal of Hypertension, Ltd.