ABSTRACT
In recent years, considerable resources have been devoted to research into the genetics of coronary heart disease (CHD). The major discoveries have generally been in the elucidation of the genes involved in monogenic disorders of lipoprotein metabolism. An outstanding example is the role of the low density lipoprotein (LDL) receptor in familial hypercholesterolaemia (FH). However, even the most liberal estimate would attribute fewer than 1 in 20 heart attacks under the age of 60 to FH.1 That premature CHD runs in families far more commonly than this is the everyday experience of physicians and cardiologists. Prospective epidemiological studies using multivariate analysis suggest that this familial clustering of CHD can be largely explained on the basis of the established risk factors: LDL cholesterol, high density lipoprotein (HDL) cholesterol, blood pressure, cigarette smoking and glucose intolerance.2 Clearly, much of the association of coronary atheroma with family history is likely to be the result of a shared family environment and dietary and social habits. It might also be concluded that any genetic influence not operating through these risk factors must make only a small contribution to premature CHD. This, however, need not be the case if it is considered that the genetic component of CHD frequently involves the combined effect of more than a single gene (polygenic).
