GENETIC VARIATIONS IN THE APOLIPOPROTEIN- B GENE

It is well known that coronary heart disease (CHD) is multifactorial, with environmental and inherited risk factors both playing a role. Apo lipoprotein B (apo B) is of major importance in lipoprotein metabolism and might play a central role in atherogenesis. The apo B gene is the obvious candidate gene to study the relations between lipid concentra tions and CHD. Some rare mutations in the apo B gene affect plasma cho lesterol levels, leading to either familial hypobetalipoproteinemia or familial defective apolipoprotein B100. Other frequent polymorphisms have little biological effect but, because of their high frequency, mi ght contribute to the development of CHD in a given population. Many a po B gene polymorphisms are associated with variations in plasma lipid concentrations, including the response of plasma lipids to dietary in tervention, and peripheral and coronary atherosclerosis. Age, body mas s index and gender affect the degree and nature of the association bet ween apo B genetic markers and normal lipid and lipoprotein levels. Ho wever, negative and contradictory results have also been reported. One likely explanation is differences between studies, including populati ons of different geographic origin, arbitrary definition of cases and controls and multiple criteria for CHD. Future work on the effect of t he apo B locus on hyperlipidaemia and atherosclerosis must involve lar ge numbers of patients belonging to carefully defined populations. Pro spective studies using a combination of genetic markers in well-define d populations should lead to firm conclusions on the role of apo B in atherogenesis and coronary heart disease.