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Gene Review

APOA2  -  apolipoprotein A-II

Homo sapiens

Synonyms: Apo-AII, ApoA-II, Apolipoprotein A-II, Apolipoprotein A2, apoAII
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Disease relevance of APOA2


Psychiatry related information on APOA2


High impact information on APOA2


Chemical compound and disease context of APOA2


Biological context of APOA2


Anatomical context of APOA2

  • To determine the apolipoprotein specificity of high density lipoprotein (HDL) receptor, apolipoprotein A-I (apo-AI) and apolipoprotein A-II (apo-AII) purified from high density lipoprotein3 (HDL3) were reconstituted into dimyristoyl phosphatidylcholine vesicles (DMPC) and their ability to bind to luteinized rat ovarian membranes was examined [17].
  • Whereas nontransgenic HDL protected against oxidized LDL induction of adhesion molecules in endothelial cells, HDL from apoA-II transgenic mice was proinflammatory [18].
  • The macrophage-to-smooth muscle cell ratio of lesions was 2.1-fold higher in apo-I/apoA-II mice than in apoA-I mice (P<0.01) [19].
  • ApoAII gene expression was demonstrated in adult human liver and HepG2 cells but not in human small intestine [20].
  • To determine the association between the -265 T to C substitution in the apolipoprotein A-II (APOA-II) gene and levels of visceral adipose tissue (VAT) in a group of premenopausal African-American and white women, we genotyped 237 women (115 African-American and 122 white) for this polymorphism [21].

Associations of APOA2 with chemical compounds

  • Human and murine apolipoprotein A-II differently affect glucose metabolism and insulin resistance [2].
  • Purified human apoA-II was incorporated into sonicated, spherical LpA-I particles containing apoA-I, phospholipids, and various amounts of triacylglycerol (TG), diacylglycerol (DG), and/or free cholesterol [22].
  • Human apolipoprotein A-II associates with triglyceride-rich lipoproteins in plasma and impairs their catabolism [23].
  • ApoA-II isolated from human plasma high density lipoprotein (HDL) by column chromatography migrated as a single band on polyacrylamide disc gel electrophoresis, had the appropriate amino acid composition, and provoked the production of monospecific antisera [24].
  • In assays, (0.05 M barbital buffer, 0.01% Triton X-100, pH 8.6) over 90% of (125)I-ApoA-II was bound by excess first antibody and over 95% was displaced by excess "cold" ApoA-II [24].

Physical interactions of APOA2

  • We have also found that the (GU) repeats in the apoA-II context bind the splicing factor TDP-43 and interfere with exon 3 definition [25].

Regulatory relationships of APOA2

  • Apolipoprotein A-II inhibits high density lipoprotein remodeling and lipid-poor apolipoprotein A-I formation [26].
  • In addition, apoA-II enhances the ability of reconstituted LpA-I particles to inhibit VLDL-TG hydrolysis by HL [22].
  • However, when the same amounts (0.1-3.0 nmol/assay) of apo A-II were incorporated together with apo A-I (0.8 nmol/assay) into the liposome, apo A-II significantly stimulated LCAT activity as compared to activity obtained with incorporation of apo A-I alone [27].

Other interactions of APOA2

  • Multipoint analysis between VP, SPTA1, APOA2 and D1S194 gave the maximum LOD score of 6.62 at APOA2, which has been physically mapped to 1q21-q23 [28].
  • CETP remodeled approximately 32% (A-I/A-II)rHDL into small but not large particles [26].
  • We used linkage analysis with polymorphic CA repeats to test for the involvement of two candidate loci, APOA2 and ACTN2 [29].
  • The average normolipidemic concentration of ApoA-I associated with ApoA-II in 50 women was 790 mg/L; in 50 men, it was 788 mg/L [30].
  • The apolipoprotein profile of all patient groups was characterized by significantly reduced levels of apolipoprotein (Apo)A-I and ApoA-II and significantly increased levels of ApoC-III [31].

Analytical, diagnostic and therapeutic context of APOA2


  1. Microsatellite DNA assays reveal an allelic imbalance in p16(Ink4), GALT, p53, and APOA2 loci in patients with endometriosis. Goumenou, A.G., Arvanitis, D.A., Matalliotakis, I.M., Koumantakis, E.E., Spandidos, D.A. Fertil. Steril. (2001) [Pubmed]
  2. Apolipoprotein A-II: beyond genetic associations with lipid disorders and insulin resistance. Kalopissis, A.D., Pastier, D., Chambaz, J. Curr. Opin. Lipidol. (2003) [Pubmed]
  3. Biosynthesis of human preproapolipoprotein A-II. Gordon, J.I., Budelier, K.A., Sims, H.F., Edelstein, C., Scanu, A.M., Strauss, A.W. J. Biol. Chem. (1983) [Pubmed]
  4. Overexpression of human apolipoprotein A-II in transgenic mice does not increase their susceptibility to insulin resistance and obesity. Escolà-Gil, J.C., Blanco-Vaca, F., Julve, J. Diabetologia (2002) [Pubmed]
  5. Role of apoA-II in lipid metabolism and atherosclerosis: advances in the study of an enigmatic protein. Blanco-Vaca, F., Escolà-Gil, J.C., Martín-Campos, J.M., Julve, J. J. Lipid Res. (2001) [Pubmed]
  6. The effect of alcohol on serum high density lipoprotein (HDL). A controlled experiment. Fraser, G.E., Anderson, J.T., Foster, N., Goldberg, R., Jacobs, D., Blackburn, H. Atherosclerosis (1983) [Pubmed]
  7. Serum apolipoprotein A-II, a biochemical indicator of alcohol abuse. Puchois, P., Fontan, M., Gentilini, J.L., Gelez, P., Fruchart, J.C. Clin. Chim. Acta (1984) [Pubmed]
  8. Low levels of serum apolipoprotein A I and A II in senile dementia. Kuriyama, M., Takahashi, K., Yamano, T., Hokezu, Y., Togo, S., Osame, M., Igakura, T. Jpn. J. Psychiatry Neurol. (1994) [Pubmed]
  9. Linkage of familial combined hyperlipidaemia to chromosome 1q21-q23. Pajukanta, P., Nuotio, I., Terwilliger, J.D., Porkka, K.V., Ylitalo, K., Pihlajamäki, J., Suomalainen, A.J., Syvänen, A.C., Lehtimäki, T., Viikari, J.S., Laakso, M., Taskinen, M.R., Ehnholm, C., Peltonen, L. Nat. Genet. (1998) [Pubmed]
  10. A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction. Stampfer, M.J., Sacks, F.M., Salvini, S., Willett, W.C., Hennekens, C.H. N. Engl. J. Med. (1991) [Pubmed]
  11. Increased concentrations of cholestanol and apolipoprotein B in the cerebrospinal fluid of patients with cerebrotendinous xanthomatosis. Effect of chenodeoxycholic acid. Salen, G., Berginer, V., Shore, V., Horak, I., Horak, E., Tint, G.S., Shefer, S. N. Engl. J. Med. (1987) [Pubmed]
  12. Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor. Vu-Dac, N., Schoonjans, K., Kosykh, V., Dallongeville, J., Fruchart, J.C., Staels, B., Auwerx, J. J. Clin. Invest. (1995) [Pubmed]
  13. Human ApoA-II inhibits the hydrolysis of HDL triglyceride and the decrease of HDL size induced by hypertriglyceridemia and cholesteryl ester transfer protein in transgenic mice. Zhong, S., Goldberg, I.J., Bruce, C., Rubin, E., Breslow, J.L., Tall, A. J. Clin. Invest. (1994) [Pubmed]
  14. Opposite effects of plasma from human apolipoprotein A-II transgenic mice on cholesterol efflux from J774 macrophages and Fu5AH hepatoma cells. Fournier, N., Cogny, A., Atger, V., Pastier, D., Goudouneche, D., Nicoletti, A., Moatti, N., Chambaz, J., Paul, J.L., Kalopissis, A.D. Arterioscler. Thromb. Vasc. Biol. (2002) [Pubmed]
  15. Assignment of a gene (NEMI) for autosomal dominant nemaline myopathy to chromosome I. Laing, N.G., Majda, B.T., Akkari, P.A., Layton, M.G., Mulley, J.C., Phillips, H., Haan, E.A., White, S.J., Beggs, A.H., Kunkel, L.M. Am. J. Hum. Genet. (1992) [Pubmed]
  16. A candidate gene study in low HDL-cholesterol families provides evidence for the involvement of the APOA2 gene and the APOA1C3A4 gene cluster. Lilja, H.E., Soro, A., Ylitalo, K., Nuotio, I., Viikari, J.S., Salomaa, V., Vartiainen, E., Taskinen, M.R., Peltonen, L., Pajukanta, P. Atherosclerosis (2002) [Pubmed]
  17. Binding of apolipoprotein A-I and A-II after recombination with phospholipid vesicles to the high density lipoprotein receptor of luteinized rat ovary. Hwang, J., Menon, K.M. J. Biol. Chem. (1985) [Pubmed]
  18. In vivo interactions of apoA-II, apoA-I, and hepatic lipase contributing to HDL structure and antiatherogenic functions. Hedrick, C.C., Castellani, L.W., Wong, H., Lusis, A.J. J. Lipid Res. (2001) [Pubmed]
  19. Arg123-Tyr166 domain of human ApoA-I is critical for HDL-mediated inhibition of macrophage homing and early atherosclerosis in mice. Holvoet, P., Peeters, K., Lund-Katz, S., Mertens, A., Verhamme, P., Quarck, R., Stengel, D., Lox, M., Deridder, E., Bernar, H., Nickel, M., Theilmeier, G., Ninio, E., Phillips, M.C. Arterioscler. Thromb. Vasc. Biol. (2001) [Pubmed]
  20. The human apolipoprotein AII gene: structural organization and sites of expression. Knott, T.J., Wallis, S.C., Robertson, M.E., Priestley, L.M., Urdea, M., Rall, L.B., Scott, J. Nucleic Acids Res. (1985) [Pubmed]
  21. Apolipoprotein A-II polymorphism and visceral adiposity in African-American and white women. Lara-Castro, C., Hunter, G.R., Lovejoy, J.C., Gower, B.A., Fernández, J.R. Obes. Res. (2005) [Pubmed]
  22. Apolipoprotein A-II regulates HDL stability and affects hepatic lipase association and activity. Boucher, J., Ramsamy, T.A., Braschi, S., Sahoo, D., Neville, T.A., Sparks, D.L. J. Lipid Res. (2004) [Pubmed]
  23. Human apolipoprotein A-II associates with triglyceride-rich lipoproteins in plasma and impairs their catabolism. Dugu??-Pujol, S., Rousset, X., Pastier, D., Quang, N.T., Pautre, V., Chambaz, J., Chabert, M., Kalopissis, A.D. J. Lipid Res. (2006) [Pubmed]
  24. Apolipoprotein A-II content of human plasma high density lipoproteins measured by radioimmunoassay. Schonfeld, G., Chen, J., McDonnell, W.F., Jeng, I. J. Lipid Res. (1977) [Pubmed]
  25. Depletion of TDP 43 overrides the need for exonic and intronic splicing enhancers in the human apoA-II gene. Mercado, P.A., Ayala, Y.M., Romano, M., Buratti, E., Baralle, F.E. Nucleic Acids Res. (2005) [Pubmed]
  26. Apolipoprotein A-II inhibits high density lipoprotein remodeling and lipid-poor apolipoprotein A-I formation. Rye, K.A., Wee, K., Curtiss, L.K., Bonnet, D.J., Barter, P.J. J. Biol. Chem. (2003) [Pubmed]
  27. Stimulation of lecithin:cholesterol acyltransferase activity by apolipoprotein A-II in the presence of apolipoprotein A-I. Chen, C.H., Albers, J.J. Eur. J. Biochem. (1986) [Pubmed]
  28. Partial characterization and assignment of the gene for protoporphyrinogen oxidase and variegate porphyria to human chromosome 1q23. Roberts, A.G., Whatley, S.D., Daniels, J., Holmans, P., Fenton, I., Owen, M.J., Thompson, P., Long, C., Elder, G.H. Hum. Mol. Genet. (1995) [Pubmed]
  29. Exclusion of two candidate loci for autosomal recessive nemaline myopathy. Tahvanainen, E., Beggs, A.H., Wallgren-Pettersson, C. J. Med. Genet. (1994) [Pubmed]
  30. Quantification of two different types of apolipoprotein A-I containing lipoprotein particles in plasma by enzyme-linked differential-antibody immunosorbent assay. Koren, E., Puchois, P., Alaupovic, P., Fesmire, J., Kandoussi, A., Fruchart, J.C. Clin. Chem. (1987) [Pubmed]
  31. Lipid and apolipoprotein profiles of uremic dyslipoproteinemia--relation to renal function and dialysis. Attman, P.O., Alaupovic, P. Nephron (1991) [Pubmed]
  32. Enzyme-linked immunoabsorbant assay of apolipoprotein AII in plasma, with use of a monoclonal antibody. Stein, E.A., DiPersio, L., Pesce, A.J., Kashyap, M., Kao, J.T., Srivastava, L., McNerney, C. Clin. Chem. (1986) [Pubmed]
  33. Apolipoprotein localization in isolated drusen and retinal apolipoprotein gene expression. Li, C.M., Clark, M.E., Chimento, M.F., Curcio, C.A. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  34. Drinking habits influence the relationship between apolipoprotein AII and body mass index. Hosokai, H., Tamura, S., Koyama, H., Satoh, H. J. Nutr. Sci. Vitaminol. (1993) [Pubmed]
  35. Evaluation of apolipoprotein A-II as a positional candidate gene for familial Type II diabetes, altered lipid concentrations, and insulin resistance. Elbein, S.C., Chu, W., Ren, Q., Wang, H., Hemphill, C., Hasstedt, S.J. Diabetologia (2002) [Pubmed]
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