Sitosterolemia: A gateway to new knowledge about cholesterol metabolism

Annals of Medicine

Volumn 35, Issue 7, 2003, Pages 502-511

  Berge, Knut Erik ^a  

^a ULLEVÅL UNIVERSITY HOSPITAL   (Norway)

Author keywords

ABCG5 and ABCG8; Cholesterol; Knock out; Overexpression; Plant sterols; Polymorphisms; Sitosterolemia; Transgenic

Indexed keywords

ABC TRANSPORTER; CELL NUCLEUS RECEPTOR; CHOLESTEROL; EZETIMIBE; HORMONE RECEPTOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; HYPOCHOLESTEROLEMIC AGENT; LIVER X RECEPTOR AGONIST; PHYTOSTEROL; UNCLASSIFIED DRUG;

AUTOSOMAL RECESSIVE DISORDER; BIOCHEMISTRY; CELL LINE; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL METABOLISM; DRUG EFFECT; GENE MUTATION; GENE OVEREXPRESSION; GENETIC ANALYSIS; GENETIC ASSOCIATION; HOMEOSTASIS; HUMAN; HYPERCHOLESTEROLEMIA; KNOCKOUT MOUSE; METABOLIC DISORDER; MOLECULAR DYNAMICS; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; SCIENCE; SITOSTEROLEMIA; TRANSCRIPTION REGULATION; TRANSGENIC MOUSE;

ANIMALS; ATP-BINDING CASSETTE TRANSPORTERS; CHOLESTEROL; CHOLESTEROL, HDL; CHOLESTEROL, LDL; HUMANS; LIPOPROTEINS; RECEPTORS, CYTOPLASMIC AND NUCLEAR; SITOSTEROLS;

EID: 0242660388     PISSN: 07853890     EISSN: None     Source Type: Journal    
DOI: 10.1080/07853890310014588     Document Type: Review

References (74)

1. Weihrauch JL, Gardner JM. Sterol content of foods of plant origin. J Am Diet Assoc 1978;73:39-47.
2. Fedeli E, Lanzani A, Capella P, Jacini G. Triterpene alchols and sterols of vegetable oils. J Am Oil Chem Soc 1966;43:254.
3. Hidaka H, Nakamura T, Aoki T, Kojima H, Nakajima Y, Kosugi K et al. Increased plasma plant sterol levels in heterozygotes with sitosterolemia and xanthomatosis. J Lipid Res 1990;31:881-8.
4. Salen G, Ahrens EH Jr, Grundy SM. Metabolism of beta-sitosterol in man. J Clin Invest 1970;49:952-67.
5. Heinemann T, Axtmann G, von Bergmann K. Comparison of intestinal absorption of cholesterol with different plant sterols in man. Eur J Clin Invest 1993;23:827-31.
6. Miettinen TA, Tilvis RS, Kesaniemi YA. Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population. Am J Epidemiol 1990;131:20-31.
7. Lutjohann D, von Bergmann K. Phytosterolaemia: diagnosis, characterization and therapeutical approaches. Ann Med 1997;29:181-84.
8. Glueck CJ, Speirs J, Tracy T, Streicher P, Illig E, Vandegrift J. Relationships of serum plant sterols (phytosterols) and cholesterol in 595 hypercholesterolemic subjects, and familial aggregation of phytosterols, cholesterol, and premature coronary heart disease in hyperphytosterolemic probands and their first-degree relatives. Metabolism 1991;40:842-8.
9. Chawla A, Repa JJ, Evans RM, Mangelsdorf DJ. Nuclear receptors and lipid physiology: opening the X-files. Science 2001;294:1866-70.
10. http://nutrigene.4t.com/humanabc.htm.
11. Allikmets R, Gerrard B, Hutchinson A, Dean M. Characterization of the human ABC superfamily: isolation and mapping of 21 new genes using the expressed sequence tags database. Hum Mol Genet 1996;10:1649-55.
12. Walker JE, Saraste M, Runswick MJ, Gay NJ. Distantly related sequences in the alpha-and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J 1982;1:945-51.
13. Rommens JM, Iannuzzi MC, Kerem B, Drumm ML, Melmer G, Dean M et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 1989;245:1059-65.
14. Brooks-Wilson A, Marcil MM, Clee SM, Zhang L-H, Roomp K, van Dam M et al. Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat Genet 1999;22:336-45.
15. Bodzioch M, Orsó E, Klucken J, Langmann T, Böttcher A, Diederich W et al. The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease. Nat Genet 1999; 22:347-51.
16. Rust S, Rosier M, Funke H, Real J, Amoura Z, J-C Piette J-C et al. Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1. Nat Genet 1999;22:352-5.
17. Bhatracharyya AK, Connor WE. Beta-sitosterolemia and xanthomatosis. A newly described lipid storage disease in two sisters. J Clin Invest 1974;53:1033-43.
18. Lee MH, Lu K, Patel SB. Genetic basis of sitosterolemia. Curr Opin Lipidol 2001;12:141-9.
19. Hidaka H, Sugiura H, Nakamura T, Kojima H, Fujita M, Sugie N et al. Beta-sitosterolemia with generalized eruptive xanthomatosis. Endocr J 1997;44:59-64.
20. Miettinen TA. Phytosterolaemia, xanthomatosis and premature atherosclerotic arterial disease: a case with high plant sterol absorption, impaired sterol elimination and low cholesterol synthesis. Eur J Clin Invest 1980;10:27-35.
21. Wang C, Lin HJ, Chan TK, Salen G, Chan WC, Tse TF. A unique patient with coexisting cerebrotendinous xanthomatosis and beta-sitosterolemia. Am J Med 1981;71:313-9.
22. Skrede B, Bjorkhem I, Bergesen O, Kayden HJ, Skrede S. The presence of 5 alpha-sitostanol in the serum of a patient with phytosterolemia, and its biosynthesis from plant steroids in rats with bile fistula. Biochim Biophys Acta 1985;836:368-75.
23. Mymin D, Wang J, Frohlich J, Hegele RA. Aortic xanthomatosis with coronary ostial occlusion child homozygous for a nonsense mutation in ABCG8. Circulation 2003;107: 791.
24. Kwiterovich PO Jr, Bachorik PS, Smith HH, McKusick VA, Connor WE, Teng B et al. Hyperapobetalipoproteinaemia in two families with xanthomas and phytosterolaemia. Lancet 1981;1:466-9.
25. Grahlke BK. Xanthomas of the Achilles tendon as the cardinal symptomes of sitosterolemia. Dtsch Med Wochensschr 1991;116:335-8.
26. Salen G, Horak I, Rothkopf M, Cohen JL, Speck J, Tint GS et al. Lethal atherosclerosis associated with abnormal plasma and tissue sterol composition in sitosterolemia with xanthomatosis. J Lipid Res 1985;26:1126-33.
27. Salen G, Shefer S, Nguyen L, Ness GC, Tint GS, Shore V. Sitosterolemia. J Lipid Res 1992;33:945-55.
28. Sudhop T, Gottwald BM, von Bergmann K. Serum plant sterols as a potential risk factor for coronary heart disease. Metabolism 2002;51:1519-21.
29. Salen G, Kwiterovich PO Jr, Shefer S, Tint GS, Horak I, Shore V et al. Increased plasma cholestanol and 5 alpha-saturated plant sterol derivatives in subjects with sitosterolemia and xanthomatosis. J Lipid Res 1985;26:203-9.
30. Salen G, Shore V, Tint GS, Forte T, Shefer S, Horak I et al. Increased sitosterol absorption, decreased removal, and expanded body pools compensate for reduced cholesterol synthesis in sitosterolemia with xanthomatosis. J Lipid Res 1989;30:1319-30.
31. Bhattacharyya AK, Connor WE, Lin DS, McMurry MM, Shulman RS. Sluggish sitosterol turnover and hepatic failure to excrete sitosterol into bile cause expansion of body pool of sitosterol in patients with sitosterolemia and xanthomatosis. Arterioscler Thromb 1991;11:1287-94.
32. Gregg RE, Connor WE, Lin DS, Brewer HB Jr. Abnormal metabolism of shellfish sterols in a patient with sitosterolemia and xanthomatosis. J Clin Invest 1986;77:1864-72.
33. Salen G, Tint GS, Shefer S, Shore V, Nguyen L. Increased sitosterol absorption is offset by rapid elimination to prevent accumulation in heterozygotes with sitosterolemia. Arterioscler Thromb 1992;12:563-8.
34. Nguyen LB, Shefer S, Salen G, Ness GC, Tint GS, Zaki FG et al. A molecular defect in hepatic cholesterol biosynthesis in sitosterolemia with xanthomatosis. J Clin Invest 1990;86: 923-31.
35. Nguyen LB, Salen G, Shefer S, Bullock J, Chen T, Tint GS et al. Deficient ileal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in sitosterolemia: sitosterol is not a feedback inhibitor of intestinal cholesterol biosynthesis. Metabolism 1994;43:855-9.
36. Shefer S, Salen G, Bullock J, Nguyen LB, Ness GC, Vhao Z et al. The effect of increased hepatic sitosterol on the regulation of 3-hydroxy-3- methylglutaryl-coenzyme A reductase and cholesterol 7 alpha-hydroxylase in the rat and sitosterolemic homozygotes. Hepatology 1994;20:213-9.
37. Nguyen LB, Shefer S, Salen G, Tint SG, Batta AK. Competitive inhibition of hepatic sterol 27-hydroxylase by sitosterol: decreased activity in sitosterolemia. Proc Assoc Am Physicians 1998;110:32-9.
38. Russell DW. Nuclear orphan receptors control cholesterol catabolism. Cell 1999;97:539-42.
39. Morganroth J, Levy RI, McMahon AE, Gotto AM Jr. Pseudohomozygous type II hyperlipoproteinemia. J Pediatr 1974;85:639-43.
40. Lutjohann D, Bjorkhem I, Ose L. Phytosterolaemia in a Norwegian family: diagnosis and characterization of the first Scandinavian case. Scand J Clin Lab Invest 1996;56:229-40.
41. Alam M, Garzon MC, Salen G, Starc TJ. Tuberous xanthomas in sitosterolemia. Pediatr Dermatol 2000;17:447-9.
42. Low LC, Lin HJ, Lau KS, Kung AW, Yeung CY. Phytosterolemia and pseudohomozygous type II hypercholesterolemia in two Chinese patients. J Pediatr 1991;118:746-9.
43. Belamarich PF, Deckelbaum RJ, Starc TJ, Dobrin BE, Tint GS, Salen G. Response to diet and cholestyramine in a patient with sitosterolemia. Pediatrics 1990;86:977-81.
44. Bays H. Ezetimibe. Expert Opin Investig Drugs 2002;11: 1587-1604.
45. von Bergmann K, Salen G, Lutjohann D, Musliner T, Musser B. Ezetimibe effectively reduces serum plant sterols in patients with sitosterolemia. Atherosclerosis Suppl. 2002;3: 323.
46. Beaty TH, Kwiterovich PO Jr, Khoury MJ, White S, Bachorik PS, Smith HH et al. Genetic analysis of plasma sitosterol, apoprotein B, and lipoproteins in a large Amish pedigree with sitosterolemia. Am J Hum Genet 1986;38:492-504.
47. Berger GM, Pegoraro RJ, Patel SB, Naidu P, Rom L, Hidaka H et al. HMG-CoA reductase is not the site of the primary defect in phytosterolemia. J Lipid Res 1998;39:1046-54.
48. Patel SB, Honda A, Salen G. Sitosterolemia: exclusion of genes involved in reduced cholesterol biosynthesis. J Lipid Res 1998;39:1055-61.
49. Patel SB, Salen G, Hidaka H, Kwiterovich PO, Stalenhoef AF, Miettinen TA et al. Mapping a gene involved in regulating dietary cholesterol absorption. The sitosterolemia locus is found at chromosome 2p21. J Clin Invest 1998;102: 1041-4.
50. Repa JJ, Turley SD, Lobaccaro JA, Medina J, Li L, Lustig K et al. Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science 2000;289:1524-9.
51. Lawn RM, Wade DP, Garvin MR, Wang X, Schwartz K, Porter JG et al. The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway. J Clin Invest 1999;104:R25-31.
52. Berge KE, Tian H, Graf GA, Yu L, Grishin NV, Schultz J et al. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 2000;290:1771-5.
53. Le Saux O, Urban Z, Tschuch C, Csiszar K, Bacchelli B, Quaglino D et al. Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum. Nat Genet 2000;25:223-7.
54. Lee MH, Lu K, Hazard S, Yu H, Shulenin S, Hidaka H et al. Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Nat Genet 2001;27:79-83.
55. Lu K, Lee MH, Hazard S, Brooks-Wilson A, Hidaka H, Kojima H et al. Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively. Am J Hum Genet 2001;69:278-90.
56. Hubacek JA, Berge KE, Cohen JC, Hobbs HH. Mutations in ATP-cassette binding proteins G5 (ABCG5) and G8 (ABCG8) causing sitosterolemia. Hum Mutat 2001;18:359-60.
57. Heimerl S, Langmann T, Moehle C, Mauerer R, Dean M, Beil FU et al. Mutations in the human ATP-binding cassette transporters ABCG5 and ABCG8 in sitosterolemia. Hum Mutat 2002;20:151.
58. Lam CW, Cheng AW, Tong SF, Chan YW. Novel donor splice site mutation of ABCG5 gene in sitosterolemia. Mol Genet Metab 2002;75:178-80.
59. Ikeda S, Mochizuki A, Sarker AH, Seki S. Identification of functional elements in the bidirectional promoter of the mouse Nthl1 and Tsc2 genes. Biochem Biophys Res Commun 2000;273:1063-8.
60. Pollner R, Schmidt C, Fischer G, Kuhn K, Poschl E. Cooperative and competitive interactions of regulatory elements are involved in the control of divergent transcription of human Col4A1 and Col4A2 genes. FEBS Lett 1997; 405:31-6.
61. Higgins CF. ABC transporters: from microorganisms to man. Annu Rev Cell Biol 1992;8:67-113.
62. Klein I, Sarkadi B, Varadi A. An inventory of the human ABC proteins. Biochim Biophys Acta 1999;1461:237-62.
63. Luciani MF, Denizot F, Savary S, Mattel MG, Chimini G. Cloning of two novel ABC transporters mapping on human chromosome 9. Genomics 1994;21:150-9.
64. Lu K, Lee MH, Yu H, Zhou Y, Sandell SA, Salen G et al. Molecular cloning, genomic organization, genetic variations, and characterization of murine sterolin genes Abcg5 and Abcg8. J Lipid Res 2002;43:565-78.
65. Repa JJ, Berge KE, Pomajzl C, Richardson JA, Hobbs H, Mangelsdorf DJ. Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta. J Biol Chem 2002;277:18793-800.
66. Remaley AT, Bark S, Walts AD, Freeman L, Shulenin S, Annilo T et al. Comparative genome analysis of potential regulatory elements in the ABCG5-ABCG8 gene cluster. Biochem Biophys Res Commun 2002;295:276-82.
67. Repa JJ, Dietschy JM, Turley SD. Inhibition of cholesterol absorption by SCH 58053 in the mouse is not mediated via changes in the expression of mRNA for ABCA1, ABCG5, or ABCG8 in the enterocyte. J Lipid Res 2002;43:1864-1874.
68. Yu L, Li-Hawkins J, Hammer RE, Berge KE, Horton JD, Cohen JC et al. Overexpression of ABCGS and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol. J Clin Invest 2002;110:671-80.
69. Yu L, Hammer RE, Li-Hawkins J, Von Bergmann K, Lutjohann D, Cohen JC et al. Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion. Proc Natl Acad Sci 2002;99:16237-42.
70. Graf GA, Li WP, Gerard RD, Gelissen I, White A, Cohen JC et al. Coexpression of ATP-binding cassette proteins ABCGS and ABCGS permits their transport to the apical surface. J Clin Invest 2002;110:659-69.
71. Iida A, Saito S, Sekine A, Mishima C, Kitamura Y, Kondo K et al. Catalog of 605 single-nucleotide polymorphisms (SNPs) among 13 genes encoding human ATP-binding cassette transporters: ABCA4, ABCA7, ABCA8, ABCD1, ABCD3, ABCD4, ABCE1, ABCF1, ABCG1, ABCG2, ABCG4, ABCG5, and ABCG8. J Hum Genet 2002;47:285-310.
72. Berge KE, von Bergmann K, Lutjohann D, Guerra R, Grundy SM, Hobbs HH et al. Heritability of plasma noncholesterol sterols and relationship to DNA sequence polymorphism in ABCG5 and ABCG8. J Lipid Res 2002;43:486-94.
73. Miettinen TA, Strandberg TE, Gylling H for the Finnish Investigators of the Scandinavian Simvastatin Survival Study 4 Group. Noncholesterol sterols and cholesterol lowering by long-term simvastatin treatment in coronary patients. Relation to basal serum cholestanol. Arterioslcer Thromb Vase Biol 2000;20:1340-6.
74. Weggemans RM, Zock PL, Tai ES, Ordovas JM, Molhuizen HO, Katan MB. ATP binding cassette G5 C1950G polymorphism may affect blood cholesterol concentrations in humans. Clin Genet 2002;62:226-9.