The human apolipoprotein genes

The apolipoproteins fall into two groups: the typical apolipoproteins (apo-AI, apo-AII, apo-AIV, apo-CI, apo-CII, apo-CIII and apo-E) constitute a multigene family with strong similarities in structure, genomic organization and in functional domains. The evolutionary relationship of these genes has been particularly well studied. Important work is now under way to analyse genetic variation of the apolipoprotein genes which contributes to alterations in plasma triglyceride and cholesterol levels and enhanced risk of coronary heart disease. Intensive work is also focused on understanding apolipoprotein gene regulation and it is hoped that this will contribute to understanding how plasma lipid levels are determined. Apolipoprotein B produces two distinct proteins. These have a central role in lipid metabolism. Their structure has been analyzed from studies on cDNAs and the organization of the gene determined. It remains to be determined how the apo-B gene produces two proteins, the intestinal form being half the size of the hepatic form. Studies to date indicate that this is not by the usual mechanisms of exon shuffling or post-translational processing. It might be anticipated that the smaller form is produced by a novel mechanism. As with the other apolipoproteins intensive work is now focused on the analysis of genetic variation and of the study of apo-B gene variation. Analysis of the apo-B gene may have profound implications for the diagnosis and treatment of plasma lipid abnormalities.