title: Potential effects of NPC1L1 polymorphisms in protecting against clinical disease in a chinese family with sitosterolaemia.
abstract: Sitosterolaemia is caused by mutations in either ABCG5 or ABCG8. Chinese and Japanese individuals usually have mutations in ABCG5. We herein report a known and a novel mutation in ABCG8 and their potential interaction with NPC1L1 polymorphisms in a Chinese family with sitosterolaemia. We sequenced ABCG5 and ABCG8 and measured the levels of plasma plant sterols in a 15-year-old Chinese girl with clinical sitosterolaemia (xanthomas with elevated low-density lipoprotein cholesterol (LDL-C) and plant sterols) and her apparently healthy family members. NPC1L1 was sequenced in the genetically affected sibling and other family members. A known mutation, c.490C＞T (p. Arg164(＊)), in exon 4 and a novel mutation, c.1949T＞G (p.Leu650Arg), in exon 13 of ABCG8 were detected in the proband and her sister, who had elevated sterols but low LDL-C levels and no xanthomas. The genetically affected sister, but not the proband, carried two additional heterozygous changes in NPC1L1 (rs2072183 C＞G, rs2301935 A＞C), which were inherited from the mother, who also had a low LDL-C level. In this study, we detected a known and a novel mutation in ABCG8 in a Chinese patient with sitosterolaemia. The same mutations were found in her clinically normal sister, suggesting that the contrasting features with the proband may be related to different variants in NPC1L1 and/or some other undetermined lipid-related genetic factors.
authors: Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong.
authors: Miao
authors: M
authors: Hu
authors: Yuet-Ping
authors: YP
authors: Yuen
authors: Jeffrey Ss
authors: JS
authors: Kwok
authors: James F
authors: JF
authors: Griffith
authors: Brian
authors: B
authors: Tomlinson
mesh_terms: D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D002681:China; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000235:genetics*; D007410:Intestinal Diseases / Q000097:blood / Q000235:genetics*; D008052:Lipid Metabolism, Inborn Errors / Q000097:blood / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010840:Phytosterols / Q000009:adverse effects* / Q000097:blood / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012855:Sitosterols / Q000097:blood
chemical_list: C416946:ABCG8 protein, human; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D010840:Phytosterols; D012855:Sitosterols