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

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1993 Feb 15

PMID 7679504

Citations 45

Authors

D P Wade

J G Clarke

G E Lindahl

A C Liu

B R Zysow

K Meer

K Schwartz

R M Lawn

Affiliations

Soon will be listed here.

Abstract

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.

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References

Malinowski D, Sadler J, Davie E . Characterization of a complementary deoxyribonucleic acid coding for human and bovine plasminogen. Biochemistry. 1984; 23(18):4243-50. DOI: 10.1021/bi00313a035. View

Sandholzer C, Saha N, Kark J, Rees A, Jaross W, Dieplinger H . Apo(a) isoforms predict risk for coronary heart disease. A study in six populations. Arterioscler Thromb. 1992; 12(10):1214-26. DOI: 10.1161/01.atv.12.10.1214. View

Rhoads G, Dahlen G, Berg K, Morton N, Dannenberg A . Lp(a) lipoprotein as a risk factor for myocardial infarction. JAMA. 1986; 256(18):2540-4. View

Chirgwin J, Przybyla A, MacDonald R, Rutter W . Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979; 18(24):5294-9. DOI: 10.1021/bi00591a005. View

Krempler F, Kostner G, Bolzano K, SANDHOFER F . Turnover of lipoprotein (a) in man. J Clin Invest. 1980; 65(6):1483-90. PMC: 371487. DOI: 10.1172/JCI109813. View

Forsgren M, Raden B, Israelsson M, Larsson K, Heden L . Molecular cloning and characterization of a full-length cDNA clone for human plasminogen. FEBS Lett. 1987; 213(2):254-60. DOI: 10.1016/0014-5793(87)81501-6. View

Murray J, Buetow K, Donovan M, Hornung S, Motulsky A, Disteche C . Linkage disequilibrium of plasminogen polymorphisms and assignment of the gene to human chromosome 6q26-6q27. Am J Hum Genet. 1987; 40(4):338-50. PMC: 1684087. View

McLean J, Tomlinson J, Kuang W, Eaton D, Chen E, Fless G . cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature. 1987; 330(6144):132-7. DOI: 10.1038/330132a0. View

Courtois G, Morgan J, Campbell L, Fourel G, Crabtree G . Interaction of a liver-specific nuclear factor with the fibrinogen and alpha 1-antitrypsin promoters. Science. 1987; 238(4827):688-92. DOI: 10.1126/science.3499668. View

10.

Utermann G, Kraft H, Menzel H, Hopferwieser T, Seitz C . Genetics of the quantitative Lp(a) lipoprotein trait. I. Relation of LP(a) glycoprotein phenotypes to Lp(a) lipoprotein concentrations in plasma. Hum Genet. 1988; 78(1):41-6. DOI: 10.1007/BF00291232. View

11.

Castellino F, Beals J . The genetic relationships between the kringle domains of human plasminogen, prothrombin, tissue plasminogen activator, urokinase, and coagulation factor XII. J Mol Evol. 1987; 26(4):358-69. DOI: 10.1007/BF02101155. View

12.

Frank S, Klisak I, Sparkes R, Mohandas T, Tomlinson J, McLean J . The apolipoprotein(a) gene resides on human chromosome 6q26-27, in close proximity to the homologous gene for plasminogen. Hum Genet. 1988; 79(4):352-6. DOI: 10.1007/BF00282175. View

13.

Hardon E, Frain M, Paonessa G, Cortese R . Two distinct factors interact with the promoter regions of several liver-specific genes. EMBO J. 1988; 7(6):1711-9. PMC: 457158. DOI: 10.1002/j.1460-2075.1988.tb03000.x. View

14.

Laplaud P, Beaubatie L, Rall Jr S, Luc G, Saboureau M . Lipoprotein[a] is the major apoB-containing lipoprotein in the plasma of a hibernator, the hedgehog (Erinaceus europaeus). J Lipid Res. 1988; 29(9):1157-70. View

15.

Landschulz W, Johnson P, Adashi E, Graves B, McKnight S . Isolation of a recombinant copy of the gene encoding C/EBP. Genes Dev. 1988; 2(7):786-800. DOI: 10.1101/gad.2.7.786. View

16.

Drayna D, Hegele R, Hass P, Emi M, Wu L, Eaton D . Genetic linkage between lipoprotein(a) phenotype and a DNA polymorphism in the plasminogen gene. Genomics. 1988; 3(3):230-6. DOI: 10.1016/0888-7543(88)90084-5. View

17.

Maeda S, Abe A, Seishima M, Makino K, Noma A, Kawade M . Transient changes of serum lipoprotein(a) as an acute phase protein. Atherosclerosis. 1989; 78(2-3):145-50. DOI: 10.1016/0021-9150(89)90218-9. View

18.

Utermann G . The mysteries of lipoprotein(a). Science. 1989; 246(4932):904-10. DOI: 10.1126/science.2530631. View

19.

Gavish D, Azrolan N, Breslow J . Plasma Ip(a) concentration is inversely correlated with the ratio of Kringle IV/Kringle V encoding domains in the apo(a) gene. J Clin Invest. 1989; 84(6):2021-7. PMC: 304088. DOI: 10.1172/JCI114395. View

20.

Hattori M, Abraham L, Northemann W, Fey G . Acute-phase reaction induces a specific complex between hepatic nuclear proteins and the interleukin 6 response element of the rat alpha 2-macroglobulin gene. Proc Natl Acad Sci U S A. 1990; 87(6):2364-8. PMC: 53687. DOI: 10.1073/pnas.87.6.2364. View