Genetic basis of atherosclerosis: part I: new genes and pathways.

Abstract

Knowledge of genetic factors in the etiology of coronary heart disease has not so far been adequately utilized in attempts to combat premature CHD. The time has now come to utilize genetic information in a setting of family-oriented preventive medicine. This approach would greatly improve the efficiency of preventive efforts, utilizing predictive genetic testing and targeting counseling on those who need it most. 1 The optimistic predictions of the impact of genetics on the diagnosis and prevention of coronary heart disease (CHD) have not been realized, and whether DNA testing will be incorporated into clinical cardiology practice in the next decades is unclear. Most of the genetic variations identified thus far either are rare or influence traditional risk factors such as low HDL, elevated LDL, high blood pressure, and diabetes. Several recent advances, however, make a case for renewed optimism (see Part I of this review). Studies in humans and mice have begun to reveal highly penetrant genetic factors that contribute to CHD susceptibility independent of traditional risk factors. As technical advances bring down genotyping costs, we may pass a threshold for the cost–benefit ratio in the near future. One important application in diagnosis is likely to involve the identification of different forms of CHD to allow individualized treatment (pharmacogenetics). The application of multilocus genotyping to assess risk or to screen populations for individuals who are highly susceptible to CHD also is a possibility. Perhaps most important, genetic studies are leading to many insights into disease mechanisms, and these studies, along with biochemical approaches, are pointing to new therapeutic concepts and treatments. Probably the most significant impact of genetic studies on medicine pertains to the development of therapies. The outstanding example is the impetus that genetic studies of familial hypercholesterolemia (FH) provided in the development of hepatic hydroxymethyl glutaryl coenzyme …