ABCG8 缺陷导致 GBD4 和 Sitosterolemia
中文名称
通路描述
ABCG8 (也称为 sterolin-2) 是 ATP 结合型 G 亚家族成员 8，是一种“半转运蛋白”，在内质网中与另一种半转运蛋白 ABCG5 形成复合物。该复合物转运至质膜，介导 ATP 依赖性的肠道吸收和胆汁分泌胆固醇及植物固醇 (如 Sitosterol)。这两种半转运蛋白缺陷均导致肠道细胞对胆固醇和 Sitosterol 的鉴别能力丧失，引起固醇积累并增加动脉粥样硬化风险。ABCG8 缺陷是胆结石疾病 4 (GBD4) 的原因，这是消化系统疾病之一，胆结石 (胆石症) 是 GBD 在西方的常见表现。ABCG8 缺陷还可导致 Sitosterolemia，其特征为胆固醇和植物来源固醇的无限制肠道吸收，导致高胆固醇血症和过早冠状动脉动脉粥样硬化。Sitosterolemia 患者吸收摄入 Sitosterol 的 15 至 60%，仅将少量排入胆汁。
英文描述
Defective ABCG8 causes GBD4 and sitosterolemia 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).
所含基因
1 个基因