Public health, cardiovascular disease and molecular biology

Rapid developments in molecular biology provide the tools to search for genetic markers of coronary heart disease. Already the angiotensin converting enzyme and the angiotensinogen genes have been implicated in myocardial infarction and hypertension. However, common conditions such as coronary disease raise special problems for genetics both in selection of suitable subjects and the use of informative genetic methods. Traditionally genetics has focused on the family; now it must broaden that view to identify markers that are relevant to the general community. The magnitude and complexity of the problem demands collaboration between epidemiologists, physicians, geneticists and laboratory scientists. This paper proposes a two stage approach to the genetics of coronary heart disease, beginning with affected relative pair linkage studies using the new generation gene maps to define chromosomal regions of interest. The thorough and systematic search using gene maps also offers the possibility of defining genetic markers of "hidden" coronary risk factors. In the second stage, candidate genes within these regions are examined in case-control association studies to identify simple markers that divide the population into groups with contrasting risk of coronary disease. It is important that families and cases are representative of the general population, otherwise the predictive value of the new genetic markers will be in doubt. In particular, genetic analyses should avoid the potential bias resulting from the exclusion of cases of sudden and unexpected coronary death.