[Application of genetic principles to the causal assessment of atherosclerosis]

The pathophysiological mechanisms responsible for the development of atherosclerosis are complex and influenced by numerous genetic factors [polygenic] as well as environmental factors. Specific disorders caused by single gene mutations [monogenic] may considerably enhance the risk for atherosclerosis. In such cases, other genes or environmental factors are often secondary importance. A detailed family history including a pedigree analysis may lead to the correct diagnosis; molecular genetic methods can confirm the clinical diagnosis. The association between a particular gene [candidate gene] and a disorder characterized by an increased risk for atherosclerosis can be verified indirectly by linkage analysis or directly by the detection of the gene mutation causing the disorder. Both approaches are based on the fact that a polymorphism used as a marker for a gene locus or a mutation responsible for a particular disorder may destroy or create a restriction site [restriction fragment length polymorphism, RFLP] or may modify the electrophoretic mobility of a fragment amplified by the polymerase chain reaction [PCR]. The latter property is the basis of the single-strand conformation polymorphism [SSCP] technique, followed by sequencing for the exact localization of the polymorphism or the mutation. Using these methods, other family members carrying the underlying gene defect can be identified and treated before the manifestation of their atherosclerotic lesions.