Defective ABCG8 causes GBD4 and sitosterolemia

Stable Identifier
Homo sapiens
Defective ABCG8 causes gallbladder disease 4 and sitosterolemia
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ATP-binding cassette sub-family G member 8 (ABCG8 aka sterolin-2), is a "half transporter", that forms a complex with another half transporter ABCG5 in the endoplasmic reticulum. This complex translocates to the plasma membrane to mediate the ATP-dependent intestinal absorption and facilitation of biliary secretion of cholesterol and phytosterols (eg sitosterol). Defects in either of these half transporters result in loss of enterocyte discrimination between cholesterol and sitosterol causing sterol accumulation and predisposition for atherosclerosis. Defects in ABCG8 are the cause of gallbladder disease 4 (GBD4; MIM:611465), one of the major digestive diseases. Gallstones are composed of cholesterol (cholelithiasis) and are the common manifestations of GBD in western countries (Buch et al. 2007, Rudkowska & Jones 2008, Jakulj et al. 2010). Defects in ABCG8 also cause sitosterolemia (MIM:210250), characterised by unrestricted intestinal absorption of both cholesterol and plant-derived sterols causing hypercholesterolemia and premature coronary atherosclerosis. Patients with sitosterolemia absorb between 15 and 60% of ingested sitosterol, and they excrete only a fraction into the bile (Berge et al. 2000, Othman et al. 2013, Yu et al. 2014).

Literature References
PubMed ID Title Journal Year
11099417 Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters

Berge, KE, Tian, H, Graf, GA, Yu, L, Grishin, NV, Schultz, J, Kwiterovich, P, Shan, B, Barnes, R, Hobbs, HH

Science 2000
24267242 Non-cholesterol sterols and cholesterol metabolism in sitosterolemia

Othman, RA, Myrie, SB, Jones, PJ

Atherosclerosis 2013
18522623 Polymorphisms in ABCG5/G8 transporters linked to hypercholesterolemia and gallstone disease

Rudkowska, I, Jones, PJ

Nutr. Rev. 2008
24252657 ABCG5/ABCG8 in cholesterol excretion and atherosclerosis

Yu, XH, Qian, K, Jiang, N, Zheng, XL, Cayabyab, FS, Tang, CK

Clin. Chim. Acta 2014
20581104 ABCG5/G8 polymorphisms and markers of cholesterol metabolism: systematic review and meta-analysis

Jakulj, L, Vissers, MN, Tanck, MW, Hutten, BA, Stellaard, F, Kastelein, JJ, Dallinga-Thie, GM

J. Lipid Res. 2010
17632509 A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease

Buch, S, Schafmayer, C, Völzke, H, Becker, C, Franke, A, von Eller-Eberstein, H, Kluck, C, Bässmann, I, Brosch, M, Lammert, F, Miquel, JF, Nervi, F, Wittig, M, Rosskopf, D, Timm, B, Höll, C, Seeger, M, ElSharawy, A, Lu, T, Egberts, J, Fändrich, F, Fölsch, UR, Krawczak, M, Schreiber, S, Nürnberg, P, Tepel, J, Hampe, J

Nat. Genet. 2007
Name Identifier Synonyms
atherosclerosis DOID:1936
lipid metabolism disorder DOID:3146 dyslipidemia, fatty acid metabolism disorder
cholelithiasis DOID:10211
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