The molecular biology of human apoA-I, apoA-II, apoC-II and apoB.

The application of molecular biology techniques has enabled us to determine the gene sequence, organization, transcription and processing of apolipoprotein genes. Consequently, new insights have been gained in the biosynthesis and processing of these proteins. In addition to apoA-I, apoA-II and apoC-III reported here, other apolipoprotein genes such as apoC-II and apoE genes were found to share common intron-exon organizations. The results suggest that these genes most probably arise from a common ancestral gene. Utilizing cDNA as hybridization probes, we have localized apoA-I, apoA-II, apoC-II, apoC-III, apoE and apoB to specific locations of individual chromosomes (for review, see ref. 6). There is no clear relationship between currently known physiological function and the organization of the apolipoproteins in the chromosomes with the exception of the LDL receptor and its ligand, apoE which are localized to chromosome 19. However, apoB-100, the major ligand for the LDL receptor is on chromosome 2 and not in synteny with the apoE and the LDL receptor genes. The cloning of the major human apolipoprotein genes have also allowed us to initiate studies on the molecular defects leading to various dyslipoproteinemias including Tangier disease and abetalipoproteinemia. Undoubtedly, information derived from these studies will provide the basis for future in vitro and in vivo studies on patients with dyslipoproteinemia and premature atherosclerosis.