The entire nucleic acid sequence of the human apoA-II gene has been determined. The structure of the apoA-II gene is similar to that of other apolipoproteins, like apoA-I, apoE, and apoC-III. The apoA-II gene consists as the aforementioned genes of three introns and four exons. The position of the introns is similar in all four genes. Promoter regions as well as a possible Z-DNA element have been identified. The knowledge of the structure of the gene will allow to study the expression in more detail. To better understand the processing of apoA-II its isoforms have been analyzed in human thoracic duct lymph and plasma as well as in culture media from normal hepatocytes and the hepatoma cell line HepG2. ProapoA-II and several isoforms of apoA-II including sialylated forms were identified. ProapoA-II has a strikingly basic pI of 6.79 which is caused by three additional positively charged residues as compared to mature apoA-II. The major mature isoform has a pI of 4.90. The sialoforms are more acidic and have a slightly higher apparent molecular weight. The isoform pattern in several dyslipidemias is different from the normal control. The reason for this variability is not yet fully understood. The apoB-100 gene and mRNA have been analyzed in normal subjects and abetalipoproteinemic (ABL) patients. The apoB gene is present in ABL and not structurally different from normal controls as determined by Southern blot analysis. The apoB-100 mRNA in ABL is of the same size as the normal mRNA, but its concentration is reduced. The absence of apoB from the plasma of ABL-patients, however, cannot be explained by this reduction. We conclude that the defect in ABL is post-translational and additional studies to characterize the defect are being undertaken.
