Sitosterolemia, Hypercholesterolemia, and Coronary Artery Disease.

Abstract

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.

• Authors: Hayato Tada, Atsushi Nohara, Akihiro Inazu, Nagahiko Sakuma, Hiroshi Mabuchi, Masa-Aki Kawashiri
• Journal: Journal of atherosclerosis and thrombosis (J Atheroscler Thromb) Vol. 25 Issue 9 Pg. 783-789 (Sep 01 2018) ISSN: 1880-3873 [Electronic] Japan
• PMID: 30033951 (Publication Type: Journal Article, Review)

Chemical References

• ABCG5 protein, human
• ABCG8 protein, human
• ATP Binding Cassette Transporter, Subfamily G, Member 5
• ATP Binding Cassette Transporter, Subfamily G, Member 8
• Lipoproteins
• Phytosterols
• Sitosterols
• gamma-sitosterol
• PCSK9 protein, human
• Proprotein Convertase 9

Topics

• ATP Binding Cassette Transporter, Subfamily G, Member 5 (genetics)
• ATP Binding Cassette Transporter, Subfamily G, Member 8 (genetics)
• Coronary Artery Disease (drug therapy, epidemiology)
• Heterozygote
• Humans
• Hypercholesterolemia (drug therapy, epidemiology)
• Intestinal Diseases (drug therapy, epidemiology)
• Lipid Metabolism, Inborn Errors (drug therapy, epidemiology)
• Lipoproteins (genetics)
• Mutation
• Phenotype
• Phytosterols (adverse effects, genetics)
• Polymorphism, Genetic
• Proprotein Convertase 9 (genetics)
• Sitosterols (chemistry)