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Gene Review

OLR1  -  oxidized low density lipoprotein (lectin...

Homo sapiens

Synonyms: C-type lectin domain family 8 member A, CLEC8A, LOX-1, LOX1, LOXIN, ...
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Disease relevance of OLR1


Psychiatry related information on OLR1


High impact information on OLR1


Chemical compound and disease context of OLR1


Biological context of OLR1

  • Our data suggest that genetic variation in the OLR1 gene may modify the risk of AD in an APOE*4-dependent fashion [1].
  • We screened all exons and intron-exon boundaries of the OLR1 gene for new mutations and identified three novel sequence variations in intron 4, intron 5, and the 3' untranslated region (UTR) [1].
  • OLR1 is a good candidate gene, due to its function in lipid metabolism pathways, other components of which have been previously implicated as risk factors for AD [12].
  • Macrophages from subjects carrying the "non-risk" disease haplotype at OLR1 gene have an increased expression of LOXIN at mRNA and protein level, which results in a significant reduction of apoptosis in response to oxLDL [13].
  • Association of single nucleotide polymorphisms in the oxidised LDL receptor 1 (OLR1) gene in patients with acute myocardial infarction [14].

Anatomical context of OLR1


Associations of OLR1 with chemical compounds


Physical interactions of OLR1

  • Taking all of the above findings together, ox-HDL activates NF-kappa B via binding to LOX-1 on the cell surface, followed by enhancement of intracellular ROS production in endothelial cells [20].
  • Together, cilostazol suppresses RLP-stimulated increased monocyte adhesion to HUVECs by suppression of LOX-1 receptor-coupled NF-kappaB-dependent nuclear transcription via mediation of the maxi-K channel opening [21].

Enzymatic interactions of OLR1


Regulatory relationships of OLR1

  • Anti-LOX-1 antibody reversed ox-LDL-stimulated MMP-3 synthesis to control levels [4].
  • The alteration of the responsiveness of LOX-1 expression to histamine was related to suppressed expression of the H2 receptor in THP-1 macrophages [9].
  • Whether CRP may regulate endothelial LOX-1 and induce endothelial dysfunction through this receptor is unknown [24].
  • In hypertensive animals, not only antihypertensive drugs but also antioxidant agents suppress the LOX-1 overexpression [25].
  • The effects of ox-LDL, but not TNFalpha, on MGP and BMP2 expression were inhibited by pretreatment of cells with an antibody directed at LOX-1, a lectin-like receptor for ox-LDL (10 microg/mL) [26].

Other interactions of OLR1

  • CONCLUSION: Ox-LDL, principally mediated by LOX-1, enhanced MMP-3 production in articular chondrocytes [4].
  • Whereas recombinant full-length DECTIN-1 and LOX-1 are transported to the cell surface, CLEC-1 proteins accumulate in perinuclear compartments [16].
  • Because of its close proximity to the A2M gene and because it is abundantly expressed in the brain, we reasoned that the oxidized LDL-receptor 1 (OLR1) gene could be a candidate gene for AD [1].
  • Histamine increases the expression of LOX-1 via H2 receptor in human monocytic THP-1 cells [9].
  • However, Abeta(40), Abeta(42), Abeta total, and Tau loads or the level of microglial cell activation were not modulated by the 3'-UTR OLR1 polymorphisms [15].

Analytical, diagnostic and therapeutic context of OLR1


  1. Investigation of oxidized LDL-receptor 1 (OLR1) as the candidate gene for Alzheimer's disease on chromosome 12. Luedecking-Zimmer, E., DeKosky, S.T., Chen, Q., Barmada, M.M., Kamboh, M.I. Hum. Genet. (2002) [Pubmed]
  2. Oxidized LDL receptor gene (OLR1) is associated with the risk of myocardial infarction. Tatsuguchi, M., Furutani, M., Hinagata, J., Tanaka, T., Furutani, Y., Imamura, S., Kawana, M., Masaki, T., Kasanuki, H., Sawamura, T., Matsuoka, R. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  3. Genetic variation in lectin-like oxidized low-density lipoprotein receptor 1 (LOX1) gene and the risk of coronary artery disease. Chen, Q., Reis, S.E., Kammerer, C., Craig, W.Y., LaPierre, S.E., Zimmer, E.L., McNamara, D.M., Pauly, D.F., Sharaf, B., Holubkov, R., Bairey Merz, C.N., Sopko, G., Bontempo, F., Kamboh, M.I. Circulation (2003) [Pubmed]
  4. Lectin-like oxidized low-density lipoprotein receptor 1 mediates matrix metalloproteinase 3 synthesis enhanced by oxidized low-density lipoprotein in rheumatoid arthritis cartilage. Kakinuma, T., Yasuda, T., Nakagawa, T., Hiramitsu, T., Akiyoshi, M., Akagi, M., Sawamura, T., Nakamura, T. Arthritis Rheum. (2004) [Pubmed]
  5. An endothelial receptor for oxidized low-density lipoprotein. Sawamura, T., Kume, N., Aoyama, T., Moriwaki, H., Hoshikawa, H., Aiba, Y., Tanaka, T., Miwa, S., Katsura, Y., Kita, T., Masaki, T. Nature (1997) [Pubmed]
  6. Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation. Delneste, Y., Magistrelli, G., Gauchat, J., Haeuw, J., Aubry, J., Nakamura, K., Kawakami-Honda, N., Goetsch, L., Sawamura, T., Bonnefoy, J., Jeannin, P. Immunity (2002) [Pubmed]
  7. Lipoxygenase is involved in the control of potato tuber development. Kolomiets, M.V., Hannapel, D.J., Chen, H., Tymeson, M., Gladon, R.J. Plant Cell (2001) [Pubmed]
  8. Upregulation of endothelial receptor for oxidized low-density lipoprotein (LOX-1) in cultured human coronary artery endothelial cells by angiotensin II type 1 receptor activation. Li, D.Y., Zhang, Y.C., Philips, M.I., Sawamura, T., Mehta, J.L. Circ. Res. (1999) [Pubmed]
  9. Histamine increases the expression of LOX-1 via H2 receptor in human monocytic THP-1 cells. Tanimoto, A., Murata, Y., Nomaguchi, M., Kimura, S., Arima, N., Xu, H., Hamada, T., Sasaguri, Y. FEBS Lett. (2001) [Pubmed]
  10. Critical role of bradykinin-eNOS and oxidative stress-LOX-1 pathway in cardiovascular remodeling under chronic angiotensin-converting enzyme inhibition. Kobayashi, N., Honda, T., Yoshida, K., Nakano, S., Ohno, T., Tsubokou, Y., Matsuoka, H. Atherosclerosis (2006) [Pubmed]
  11. Pravastatin inhibits expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in Watanabe heritable hyperlipidemic rabbits: a new pleiotropic effect of statins. Hofnagel, O., Luechtenborg, B., Eschert, H., Weissen-Plenz, G., Severs, N.J., Robenek, H. Arterioscler. Thromb. Vasc. Biol. (2006) [Pubmed]
  12. No association between polymorphisms in the lectin-like oxidised low density lipoprotein receptor (ORL1) gene on chromosome 12 and Alzheimer's disease in a UK cohort. Pritchard, A., St Clair, D., Lemmon, H., Mann, D.M., Lendon, C. Neurosci. Lett. (2004) [Pubmed]
  13. In vivo and in vitro studies support that a new splicing isoform of OLR1 gene is protective against acute myocardial infarction. Mango, R., Biocca, S., del Vecchio, F., Clementi, F., Sangiuolo, F., Amati, F., Filareto, A., Grelli, S., Spitalieri, P., Filesi, I., Favalli, C., Lauro, R., Mehta, J.L., Romeo, F., Novelli, G. Circ. Res. (2005) [Pubmed]
  14. Association of single nucleotide polymorphisms in the oxidised LDL receptor 1 (OLR1) gene in patients with acute myocardial infarction. Mango, R., Clementi, F., Borgiani, P., Forleo, G.B., Federici, M., Contino, G., Giardina, E., Garza, L., Fahdi, I.E., Lauro, R., Mehta, J.L., Novelli, G., Romeo, F. J. Med. Genet. (2003) [Pubmed]
  15. Association of 3'-UTR polymorphisms of the oxidised LDL receptor 1 (OLR1) gene with Alzheimer's disease. Lambert, J.C., Luedecking-Zimmer, E., Merrot, S., Hayes, A., Thaker, U., Desai, P., Houzet, A., Hermant, X., Cottel, D., Pritchard, A., Iwatsubo, T., Pasquier, F., Frigard, B., Conneally, P.M., Chartier-Harlin, M.C., DeKosky, S.T., Lendon, C., Mann, D., Kamboh, M.I., Amouyel, P. J. Med. Genet. (2003) [Pubmed]
  16. A novel cluster of lectin-like receptor genes expressed in monocytic, dendritic and endothelial cells maps close to the NK receptor genes in the human NK gene complex. Sobanov, Y., Bernreiter, A., Derdak, S., Mechtcheriakova, D., Schweighofer, B., Düchler, M., Kalthoff, F., Hofer, E. Eur. J. Immunol. (2001) [Pubmed]
  17. Glucose enhances endothelial LOX-1 expression: role for LOX-1 in glucose-induced human monocyte adhesion to endothelium. Li, L., Sawamura, T., Renier, G. Diabetes (2003) [Pubmed]
  18. Linoleic acid increases lectin-like oxidized LDL receptor-1 (LOX-1) expression in human aortic endothelial cells. Maingrette, F., Renier, G. Diabetes (2005) [Pubmed]
  19. Lectin-like oxidized low-density lipoprotein (LDL) receptor (LOX-1)-mediated pathway and vascular oxidative injury in older-age rat renal transplants. Bräsen, J.H., Nieminen-Kelhä, M., Markmann, D., Malle, E., Schneider, W., Neumayer, H.H., Budde, K., Luft, F.C., Dragun, D. Kidney Int. (2005) [Pubmed]
  20. NF-kappa B activation in endothelial cells treated with oxidized high-density lipoprotein. Matsunaga, T., Hokari, S., Koyama, I., Harada, T., Komoda, T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  21. Cilostazol prevents remnant lipoprotein particle-induced monocyte adhesion to endothelial cells by suppression of adhesion molecules and monocyte chemoattractant protein-1 expression via lectin-like receptor for oxidized low-density lipoprotein receptor activation. Park, S.Y., Lee, J.H., Kim, Y.K., Kim, C.D., Rhim, B.Y., Lee, W.S., Hong, K.W. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  22. Expression of lectin-like oxidized LDL receptor-1 in smooth muscle cells after vascular injury. Eto, H., Miyata, M., Kume, N., Minami, M., Itabe, H., Orihara, K., Hamasaki, S., Biro, S., Otsuji, Y., Kita, T., Tei, C. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  23. Induction of the oxLDL receptor LOX-1 by endothelin-1 in human endothelial cells. Morawietz, H., Duerrschmidt, N., Niemann, B., Galle, J., Sawamura, T., Holtz, J. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  24. C-reactive protein enhances LOX-1 expression in human aortic endothelial cells: relevance of LOX-1 to C-reactive protein-induced endothelial dysfunction. Li, L., Roumeliotis, N., Sawamura, T., Renier, G. Circ. Res. (2004) [Pubmed]
  25. Role of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in the development of hypertensive organ damage. Ando, K., Fujita, T. Clin. Exp. Nephrol. (2004) [Pubmed]
  26. Regulatory role of endothelium in the expression of genes affecting arterial calcification. Cola, C., Almeida, M., Li, D., Romeo, F., Mehta, J.L. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
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