Journal
CURRENT OPINION IN LIPIDOLOGY
Volume 32, Issue 2, Pages 117-122Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOL.0000000000000734
Keywords
ABCG5; ABCG8; sitosterolemia; xenosterols
Ask authors/readers for more resources
ABCG5 and ABCG8 variants play a significant role in human diseases, with recent research showing a higher prevalence than previously thought, especially in patients with hypercholesterolemia. Measuring xenosterol levels to screen for variants and tailoring treatment accordingly may help reduce cardiovascular risk.
Purpose of review In this review, we summarize the genetics and mechanisms of sitosterolemia and sterol trafficking, and provide an update on the understanding of the prevalence of ABCG5 and ABCG8 variants and their role in human disease. Recent findings Defects in ABCG5/G8 result in the accumulation of xenosterols. It had been previously thought that near total LoF of one of the proteins was required to cause pathology. However, recently there was the first report of a patient with Sitosterolemia who was heterozygous for mutations in both genes. Moreover, large population studies have demonstrated the even simple heterozygous carriers are associated with altered lipid profiles and cardiovascular risk. Broader screening has added to the rapidly growing list of gene variants indicating that the prevalence of ABCG5/G8 variants is higher than previous thought, especially in patients with hypercholesterolemia. These findings support a strategy of measuring xenosterol levels in patients with hypercholesterolemia to screen for ABCG5/G8 variants, and then tailoring treatment with a sterol absorption inhibitor, like ezetimibe, where indicated. Xenosterol trafficking affects remnant clearance and maybe pathogenically linked to the increased risk of atherosclerosis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available