Genetic aspects of cerebrovascular disease.

In the past conventional wisdom held that stroke and other forms of cardiovascular disease were due primarily to environmental factors and that genetic background played a relatively minor role in disease pathogenesis. However, recent discoveries in the fields of molecular and population genetics have suggested the need to reexamine the role of genetic factors in the pathogenesis of vascular disease. Research into the genetics of stroke presents some unique challenges since stroke is a heterogeneous disease with multiple risk factors. However, such studies provide an opportunity to elucidate the etiology of stroke at a molecular level and to attempt true primary prevention. This article reviews some of the principles of inherited disorders and genetic research techniques and applies the concepts to the study of the genetics of specific stroke types. Over 3,000 genetic disorders have been described in man, but the gene defect responsible for a specific disease has been identified for only a handful of diseases. Many genetic diseases are termed "simple" diseases: they follow a clear Mendelian pattern of inheritance (e.g., autosomal dominant, X-luiked recessive) and are due to a defect in only a single gene, and every individual with the gene defect will display the mutant phenotype. Examples of simple neurogenetic diseases include Huntingdon's chorea, Duchenne's muscular dystrophy, and myotonic muscular dystrophy. The "complex" genetic disorders are thought to be due to multiple gene interactions (perhaps influenced by environmental factors), with variable clinical expression of the disease phenotype. Examples include diabetes, cancer, and atherosclerosis. The study of complex genetic disorders is complicated by numerous factors: 1) Environmental factors: Extrinsic influences such as diet, smoking, and stress may be responsible for the modified expression of certain genetic traits. For example, an individual with the genetic propensity for hyperlipidemia may reduce serum cholesterol by eating a modified diet. Likewise, genetic factors may have