5' Control Regions of the Apolipoprotein(a) Gene and Members of the Related Plasminogen Gene Family

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 4; pp. 1369 - 1373
• Main Authors: Wade, David P., Clarke, John G., Lindahl, Gisela E., Liu, Alexander C., Zysow, Bernice R., Meer, Kelli, Schwartz, Karen, Lawn, Richard M.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 15-02-1993; National Acad Sciences; National Academy of Sciences
• Subjects: apolipoprotein(a); Apolipoproteins - genetics; Apoprotein(a); Base Sequence; Biochemistry; Blood; Blood plasma; Carcinoma, Hepatocellular; Complementary DNA; DNA; DNA - genetics; DNA - isolation & purification; Exons; gene families; Genes; Genomic Library; Genomics; Hep G2 cells; Humans; interleukin-6; Lipoprotein(a); Liver Neoplasms; Luciferases - genetics; Luciferases - metabolism; man; Messenger RNA; Molecular Sequence Data; Multigene Family; Oligodeoxyribonucleotides; Plasmids; plasminogen; Plasminogen - genetics; Poly A - genetics; Poly A - isolation & purification; Promoter Regions, Genetic; Proteins; Recombinant Fusion Proteins - metabolism; Regional identity; regulatory; Restriction Mapping; RNA - genetics; RNA - isolation & purification; RNA, Messenger - genetics; sequence; Sequence Homology, Nucleic Acid; transcription; Transcription, Genetic; Transfection; Tumor Cells, Cultured
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.4.1369

Elevated blood levels of apolipoprotein(a), the component of lipoprotein(a) that distinguishes it from low density lipoprotein, are a major risk factor for atherosclerosis. The apolipoprotein(a) gene is highly similar to the plasminogen gene and to at least four other genes or pseudogenes. The 5' untranslated and flanking sequences of these six genes contain extensive regions of near identity and share sequence elements involved in the initiation of transcription and translation. About 1000 base pairs of flanking DNA of each gene are sufficient to promote transcription in cultured hepatocytes. The apolipoprotein(a) gene promoter contains functional interleukin 6-responsive elements, consistent with the reported acute-phase response of apolipoprotein(a). Flanking genomic fragments of the apoliprotein(a) gene from two individuals with vastly different plasma apolipoprotein(a) concentrations have sequence differences that are reflected in differences in the rate of in vitro transcription.