Sitosterolemia, Hypercholesterolemia, and Coronary Artery Disease

• Published in: Journal of Atherosclerosis and Thrombosis Vol. 25; no. 9; pp. 783 - 789
• Main Authors: Tada, Hayato, Nohara, Atsushi, Inazu, Akihiro, Sakuma, Nagahiko, Mabuchi, Hiroshi, Kawashiri, Masa-aki
• Format: Journal Article
• Language: English
• Published: Japan Japan Atherosclerosis Society 01.09.2018
• Subjects: ABCG5; ABCG8; ATP Binding Cassette Transporter, Subfamily G, Member 5 - genetics; ATP Binding Cassette Transporter, Subfamily G, Member 8 - genetics; Coronary Artery Disease - drug therapy; Coronary Artery Disease - epidemiology; Familial hypercholesterolemia; Heterozygote; Humans; Hypercholesterolemia - drug therapy; Hypercholesterolemia - epidemiology; Intestinal Diseases - drug therapy; Intestinal Diseases - epidemiology; Lipid Metabolism, Inborn Errors - drug therapy; Lipid Metabolism, Inborn Errors - epidemiology; Lipoproteins - genetics; Mutation; Phenotype; Phytosterols - adverse effects; Phytosterols - genetics; Polymorphism, Genetic; Proprotein Convertase 9 - genetics; Review; Sitosterolemia; Sitosterols - chemistry; ABCG8; ABCG5; Familial hypercholesterolemia; Sitosterolemia
• ISSN: 1340-3478; 1880-3873; 1880-3873
• DOI: 10.5551/jat.RV17024

Sitosterolemia is a rare inherited disease characterized by increased levels of plant sterols, such as sitosterol. The cause of this disease is ATP-binding cassette (ABC) subfamily G member 5 or member 8 (ABCG5 or ABCG8, respectively) gene mutations. Recent advances in genetics have revealed that the prevalence of subjects with deleterious mutations in ABCG5 and/or ABCG8 genes could be more than 1 in ~200,000 individuals among the general population. Furthermore, accumulated evidence, including infantile cases exhibiting progression/regression of systemic xanthomas associated with LDL cholesterol levels, have shown that the elevation of LDL cholesterol seems to be the major cause of development of atherosclerosis and not the elevation of sitosterol. Regarding therapies, LDL apheresis, as well as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, could be useful for sitosterolemia, in addition to ezetimibe and/or colestimide. In this study, we provide the current understanding and future perspectives of sitosterolemia, which is currently considered an extremely rare disorder but is expected to be much more prevalent in clinical settings.