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Mapping a gene involved in regulating dietary cholesterol absorption: The sitosterolemia locus is found at chromosome 2p21
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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
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Lu K, Lee MH, Hazard S, 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; 69:276-290.
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Increased sitosterol absorption, decreased removal, and expanded body pools compensate for reduced cholesterol synthesis in sitosterolemia with xanthomatosis
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Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion
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Yu L, Hammer RE, Li-Hawkins J, et al. Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion. Proc Natl Acad Sci U S A 2002; 99:16237-16242. This study shows that disruption of Abcg5 and Abcg8 in mice results in a 30-fold increase in plasma plant sterol levels and a 2.5-fold increase in plasma cholesterol levels resulting in a similar phenotype as the human disease stiosterolemia.
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Proc Natl Acad Sci U S A
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Yu, L.1
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Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol
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Yu L, Li-Hawkins J, Hammer RE, et al. Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol. J Clin Invest 2002; 110:671-680. This study shows that overexpression of human ABCG5 and ABCG8 in a transgenic mouse results in decreased dietary cholesterol absorption, increased biliary cholesterol excretion and subsequent increased de-novo cholesterol synthesis.
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J Clin Invest
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Yu, L.1
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Small DM. Role of ABC transporters in secretion of cholesterol from liver into bile. Proc Natl Acad Sci U S A 2003; 100:4-6.
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Wittenburg H, Carey MC. Biliary cholesterol secretion by the twinned sterol half-transporters ABCG5 and ABCG8. J Clin Invest 2002; 110:605-609.
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Coexpression of ATP-binding cassette proteins ABCG5 and ABCG8 permits their transport to the apical surface
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Graf GA, Li WP, Gerard RD, et al. Coexpression of ATP-binding cassette proteins ABCG5 and ABCG8 permits their transport to the apical surface. J Clin Invest 2002; 110:659-669. This study shows that coexpression of ABCG5 and ABCG8 is required for appropriate protein trafficking to the apical surface in a polarized cell system. It assumes ABCG5 and ABCG8 form a functional heterodimer but does not show in-vivo heterodimeric function of ABCG5 and ABCG8.
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Repa JJ, Berge KE, Pomajzl C, et al. Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta. J Biol Chem 2002; 277:18793-18800. This is an in-vivo look at liver X receptor activation which results in the increased expression of Abcg5 and Abcg8 messenger RNA in mice leading to the notion that liver X receptors serve as 'sterol sensors'.
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J Biol Chem
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Repa, J.J.1
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Plat J, Mensink RP. Effects of plant sterols and stanols on lipid metabolism and cardiovascular risk. Nutr Metab Cardiovasc Dis 2001; 11:31-40.
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Nguyen TT. The cholesterol-lowering action of plant stanol esters. J Nutr 1999; 129:2109-2112.
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Moghadasian MH, Frohlich JJ. Effects of dietary phytosterols on cholesterol metabolism and atherosclerosis: clinical and experimental evidence. Am J Med 1999; 107:588-594.
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Loci on chromosomes 14 and 2, distinct from Abcg5/Abcg8, regulate plasma plant sterol levels in a C57BL/6J x CASA/Rk intercross
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Sehayek E, Duncan EM, Lutjohann D, et al. Loci on chromosomes 14 and 2, distinct from Abcg5/Abcg8, regulate plasma plant sterol levels in a C57BL/6J x CASA/Rk intercross. Proc Natl Acad Sci U S A 2002; 99:16215-16219. A very interesting paper in which genetic crossing of different mice strains results in the possibility of loci other than the STSL locus that may have an influence on plant sterol levels.
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Proc Natl Acad Sci U S A
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Sehayek, E.1
Duncan, E.M.2
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Berge KE, von Bergmann K, Lutjohann D, et al. Heritability of plasma noncholesterol sterols and relationship to DNA sequence polymorphism in ABCG5 and ABCG8. J Lipid Res 2002; 43:486-494. This is an excellent analysis of sitosterolemic patients and their families that reveals variations in plant sterol levels is highly heritable due to polymorphisms in the ABCG8 and likely ABCG5.
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(2002)
J Lipid Res
, vol.43
, pp. 486-494
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Berge, K.E.1
Von Bergmann, K.2
Lutjohann, D.3
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