Multiplex Polymerase Chain Reaction and Immobilized Probes: Application to Cardiovascular Disease

Abstract

Cardiovascular disease (CVD) is one of many common diseases for which there appear to be multiple genetic and environmental risk factors that interact with one another during the disease process. Among some families, causative mutations in certain genes have been ident ified, such as for familial hypertrophic cardiomyopathy, long-QT syndrome, and Marfan syndrome (reviewed by Maron et al. 1998); however, the association of these same genes with common forms of CVD is not fully understood. Extensive epidemiological studies have identified risk factors for disease in the general population, including age and gender, high serum cholesterol levels and hypertension, cigarette smoking, and physical inactivity (reviewed by Pasternak et al. 1996). Familial clustering (ten Kate et al. 1982) and twin studies (Marenberg et al. 1994) indicate that family history is an independent risk factor, particularly for individuals before the age of 55, and that this is not entirely explained by familial aggregation of hyperlipidemia, diabetes mellitus, obesity, and hypertension. Many premature CVD cases remain unexpl ained (Hoeg 1997), and unknown risk factors may be primarily genetic. These genetic risk factors may include the cumulative effects of common allelic variants; although individual variants may contribute only a modest increase in risk, combinations of particular alleles may confer significantly greater risk for disease.