Finding Genes for Cardiovascular Disease

Genetics studies of cardiovascular disease involve searches for genes in two general classes: causative genes and disease-susceptibility (or disease-modifying) genes. These are sought through gene-linkage analysis or candidate-gene studies, respectively. Identifying causative genes for this disease is likely several years away at best. Before that time, however, a new understanding will have been reached regarding the relationship between inherited risks and outcomes in cardiovascular disease. With the development of new technology, we also have the promise of a detailed catalogue of disease-modifying genes that may open the door to therapeutic advances.

Gene-linkage analyses involve the study of families that express the cardiovascular trait of interest. In such studies, it is important also to establish the relative risk. Relative risk is defined as the probability of developing a condition (such as cardiovascular disease) if a risk factor (such as a gene) is present, divided by the probability of developing the condition if the risk factor is absent. A relative risk greater than 4.0 (that is, a four-fold greater risk due to presence of a gene or genes) will be associated with a reasonable likelihood of success in finding associated genes, given a study of 200 sibling pairs demonstrating the condition.

One of the best-studied types of cardiovascular disease is early-onset (or premature) coronary artery disease, which has a particularly strong genetic or inherited component. The coronary arteries are those around the heart that supply it with blood. Early-onset is defined as disease presentation (as reversible heart pain, heart attack, or cardiovascular surgery) before the age of 50. Approximately 8 to 10 percent of the U.S. population with cardiovascular disease presents before age 50, according to most surveys. Based upon a number of relatively small epidemiologic studies and several genetics studies in twins, a conservative estimate of the relative risk ratio contributed by genetics to the development of early-onset cardiovascular disease is between 4.0 and 8.0. Despite the fact that it has an inherited component, the actual genes responsible for familial predisposition to early-onset coronary artery disease have been incompletely investigated and remain obscure.

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