Loss-of-function mutation R46L in the PCSK9 gene has little impact on the levels of total serum cholesterol in familial hypercholesterolemia heterozygotes

Clinica Chimica Acta

Volumn 411, Issue 3-4, 2010, Pages 229-233

  Strøm, Thea Bismo ^a   Holla, Øystein L ^a   Cameron, Jamie ^a   Berge, Knut Erik ^a   Leren, Trond P ^a  

^a OSLO UNIVERSITY HOSPITAL   (Norway)

Author keywords

Familial hypercholesterolemia; Low density lipoprotein; Low density lipoprotein receptor; Mutation; PCSK9

Indexed keywords

HIGH DENSITY LIPOPROTEIN; LOW DENSITY LIPOPROTEIN; LOW DENSITY LIPOPROTEIN RECEPTOR; PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9; SERINE PROTEINASE; UNCLASSIFIED DRUG;

ADULT; ARTICLE; CELL CULTURE; CHOLESTEROL BLOOD LEVEL; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; EXON; FAMILIAL HYPERCHOLESTEROLEMIA; FEMALE; HETEROZYGOTE; HUMAN; HUMAN CELL; INTERSTITIAL FLUID; LOSS OF FUNCTION MUTATION; MALE; PRIORITY JOURNAL; PROTEIN EXPRESSION; TRANSGENE; WESTERN BLOTTING;

ADULT; BINDING, COMPETITIVE; CELL LINE; CHOLESTEROL; FEMALE; HETEROZYGOTE; HUMANS; HYPERLIPOPROTEINEMIA TYPE II; LIPOPROTEINS, LDL; MALE; MUTATION; PROTEIN TRANSPORT; RECEPTORS, LDL; SERINE ENDOPEPTIDASES;

EID: 72449203600     PISSN: 00098981     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cca.2009.11.008     Document Type: Article

References (32)

1. Goldstein J.L., Hobbs H.H., and Brown M.S. Familial hypercholesterolemia. In: Scriver C.R., Beaudet A.L., Sly W.S., and Valle D. (Eds). The metabolic & molecular bases of inherited disease (2001), McGraw-Hill, New York 2863-2913
2. Maxwell K.N., and Breslow J.L. Adenoviral-mediated expression of PCSK9 in mice results in a low-density lipoprotein receptor knockout phenotype. Proc Natl Acad Sci USA 101 (2004) 7100-7105
3. Park S.W., Moon Y.A., and Horton J.D. Post-transcriptional regulation of low-density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9a in mouse liver. J Biol Chem 279 (2004) 50630-50638
4. Lagace T.A., Curtis D.E., Garuti R., et al. Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice. J Clin Invest 116 (2006) 2995-3005
5. Zhang D.W., Lagace T.A., Garuti R., et al. Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of the low density lipoprotein receptor decreases receptor recycling and increases degradation. J Biol Chem 282 (2007) 18602-18612
6. Qian Y.W., Schmidt R.J., Zhang Y., et al. Secreted PCSK9 downregulates low density lipoprotein receptor through receptor-mediated endocytosis. J Lipid Res 48 (2007) 1488-1498
7. Abifadel M., Rabès J.P., Devillers M., et al. Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (PCSK9) gene in cholesterol metabolism and disease. Hum Mutat 30 (2009) 520-529
8. Cameron J., Holla Ø.L., Ranheim T., Kulseth M.A., Berge K.E., and Leren T.P. Effect of mutations in the PCSK9 gene on the cell surface LDL receptors. Hum Mol Genet 15 (2006) 1551-1558
9. Hallman D.M., Srinivasan S.R., Chen W., Boerwinkle E., and Berenson G.S. Relation of PCSK9 mutations to serum low-density lipoprotein cholesterol in childhood and adulthood (from the Bogalusa Heart Study). Am J Cardiol 100 (2007) 69-72
10. Cohen J.C., Boerwinkle E., Mosley T.H., and Hobbs H.H. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 354 (2006) 1264-1272
11. Berge K.E., Ose L., and Leren T.P. Missense mutations in the PCSK9 gene are associated with hypocholesterolemia and possibly increased response to statin therapy. Arterioscler Thromb Vasc Biol 26 (2006) 1094-1100
12. Abifadel M., Varret M., Rabès J.P., et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 34 (2003) 154-156
13. Kostrzewa G., Broda G., Kurjata P., Piotrowski W., and Ploski R. Effect of protein convertase subtilisin/kexin type 9 (PCSK9) 46L gene polymorphism on LDL cholesterol concentration in a Polish adult population. Mol Genet Metab 94 (2008) 259-262
14. Scartezini M., Hubbart C., Whittall R.A., Cooper J.A., Neil A.H.W., and Humphries S.E. The PCSK9 gene R46L variant is associated with lower plasma lipid levels and cardiovascular risk in UK healthy men. Clin Sci 113 (2007) 435-441
15. Leren T.P., and Berge K.E. Identification of mutations in the apolipoprotein B-100 gene and in the PCSK9 gene as the cause of hypocholesterolemia. Clin Chim Acta 397 (2008) 92-95
16. Fasano T., Cefalù A.B., Di Leo E., et al. A novel loss of function mutation of PCSK9 gene in white subjects with low-plasma low-density lipoprotein cholesterol. Arterioscler Thromb Vasc Biol 27 (2007) 677-681
17. Friedewald W.T., Levy R.I., and Fredrickson D.S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of preparative ultracentrifuge. Clin Chem 18 (1972) 401-408
18. Tveten K., Holla Ø.L., Ranheim T., Berge K.E., Leren T.P., and Kulseth M.A. 4-Phenylbutyrate restores the functionality of a misfolded mutant low-density lipoprotein receptor. FEBS J 274 (2007) 1881-1893
19. Holla Ø.L., Cameron J., Berge K.E., Ranheim T., and Leren T.P. Degradation of the LDL receptors by PCSK9 is not mediated by a secreted protein acted upon by PCSK9 extracellularly. BMC Cell Biol 8 (2007) 9
20. Fisher T.S., Lo Surdo P., Pandit S., et al. Effects of pH and low density lipoprotein (LDL) on PCSK9-dependent LDL receptor regulation. J Biol Chem 282 (2007) 20502-20512
21. Parini P., Johansson L., Bröijersén A., Angelin B., and Rudling M. Lipoprotein profiles in plasma and interstitial fluid analyzed with an automated gel-filtration system. Eur J Clin Invest 36 (2006) 98-104
22. Sloop C.H., Dory L., and Roheim P.S. Interstitial fluid lipoproteins. J Lipid Res 28 (1987) 225-237
23. Sniderman A., Shapiro S., Marpole D., Skinner B., Teng B., and Kwiterovich Jr. P.O. Association of coronary atherosclerosis with hyperapobetalipoproteinemia [increased protein but normal cholesterol levels in human plasma low density (beta) lipoproteins]. Proc Natl Acad Sci USA 77 (1980) 604-608
24. Cameron J., Holla Ø.L., Laerdahl J.K., Kulseth M.A., Berge K.E., and Leren T.P. Mutation S462P in the PCSK9 gene reduces secretion of mutant PCSK9 without affecting the autocatalytic cleavage. Atherosclerosis 203 (2009) 161-165
25. Cameron J., Holla O.L., Laerdahl J.K., Kulseth M.A., et al. Characterization of novel mutations in the catalytic domain of the PCSK9 gene. J Intern Med 263 (2008) 420-431
26. Frank-Kamenetsky M., Grefhorst A., Anderson N.N., et al. Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc Natl Acad Sci USA 105 (2008) 11915-11920
27. Chan J.C., Piper D.E., Cao Q., et al. A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates. Proc Natl Acad Sci USA 106 (2009) 9820-9825
28. Graham M.J., Lemonidis K.M., Whipple C.P., et al. Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice. J Lipid Res 48 (2007) 763-767
29. Fouchier S.W., Sankatsing R.R., Peter J., et al. High frequency of apoB gene mutations casuing familial hypobetalipoproteinaemia in patients of Dutch and Spanish descent. J Med Genet 42 (2005) e23
30. Schonfeld G., Lin X., and Yue P. Familial hypobetalipoproteinemia: genetics and metabolism. Cell Mol Life Sci 62 (2005) 1372-1378
31. Zhao Z., Tuakli-Wosornu Y., Lagace T.A., et al. Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote. Am J Hum Genet 79 (2006) 514-523
32. Hooper A.J., Marais A.D., Tanyanyiwa D.M., and Burnett J.R. The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population. Atherosclerosis 193 (2007) 445-448