Evaluation of plasma phytosterols in sitosterolemia, their kindreds and hyperlipidemia subjects

• Published in: Journal of clinical lipidology Vol. 19; no. 1; pp. 146 - 155
• Main Authors: Ren, Xuanru, Zhang, Jun, Wang, Luya, Zhang, Yuxuan, Li, Jialu, Yu, Hao, Zheng, Zhaohai, Zhang, Yiqing, Zeng, Hesong, Chen, Yan, Wu, Junfang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2025
• Subjects: Adult; Aged; ATP Binding Cassette Transporter, Subfamily G, Member 5 - genetics; ATP Binding Cassette Transporter, Subfamily G, Member 8 - genetics; Cholesterol - blood; Female; Humans; Hypercholesterolemia - blood; Hypercholesterolemia - genetics; Hyperlipidemia; Hyperlipidemias - blood; Hyperlipidemias - genetics; Intestinal Diseases - blood; Intestinal Diseases - diagnosis; Intestinal Diseases - genetics; Kindred; Lipid Metabolism, Inborn Errors - blood; Lipid Metabolism, Inborn Errors - genetics; Lipoproteins; Male; Middle Aged; Mutation; Pedigree; Phytosterols; Phytosterols - adverse effects; Phytosterols - blood; Retrospective Studies; Single mutation carrier; Sitosterolemia; Sitosterols - blood; Young Adult; Kindred; Sitosterolemia; Hyperlipidemia; Single mutation carrier; Phytosterols
• ISSN: 1933-2874
• DOI: 10.1016/j.jacl.2024.09.002

•Mild phytosterol disruption in sitosterolemia kindred with single mutation.•A discriminative role of 7-dehydrocholesterol reductase in distinguishing hyperlipidemia and sitosterolemia kindred.•The combination of 6 phytosterols proved value than clinical lipid index in distinguishing between sitosterolemia, its single mutation kindred, and hyperlipidemia. Patients suffering from sitosterolemia with ABCG5/8 mutation typically present with early-onset or rapidly progressive atherosclerosis. Their kindreds with partial genetic deficiencies of ABCG5/8 are often considered healthy. However, discerning sitosterolemia from its familial kindreds and hyperlipidemia subjects has remained challenging. Here we retrospectively recruited 7 families including 8 individuals diagnosed with sitosterolemia subjects, and 14 kindreds carrying single gene mutations. Additionally, 17 individuals with hyperlipidemia and 130 healthy controls served as positive and negative controls, respectively. A total of 6 phytosterols combined with cholesterol absorption indices (including sitosterol, campesterol, stigmasterol, and cholestanol) and cholesterol synthesis markers (desmosterol and 7-dehydrocholesterol), was compared across the aforementioned 4 groups. As expected, the sitosterolemia subjects with double mutations demonstrated significantly elevated levels of sitosterol and other cholesterol absorption indices. Meanwhile, sitosterolemia kindreds with single gene mutation showed a similar pattern of activated cholesterol-absorption ability to the hyperlipidemia group, but not as high as the double mutation group. Notably, the cholesterol-synthesis enzyme 7-dehydrocholesterol reductase displayed an increase in the hyperlipidemia group but a decrease in the sitosterolemia kindred group, suggesting a potential discriminative role of 7-dehydrocholesterol in distinguishing between these 2 groups. The combination of phytosterols was more valuable than clinical lipid index for sitosterolemia diagnosis. Our study revealed mild disruptions of cholesterol absorption capacities in sitosterolemia kindreds with single mutations. Furthermore, the combination of 6 phytosterols proved effective in distinguishing between sitosterolemia, its single mutation carriers, and hyperlipidemia patients. [Display omitted]