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J Clin Lipidol. 2018 Jan - Feb;12(1):152-161. doi: 10.1016/j.jacl.2017.10.013. Epub 2017 Oct 27.

The association between hypercholesterolemia and sitosterolemia, and report of a sitosterolemia kindred.

Author information

1
Utah Lipid Center, Salt Lake City, UT, USA.
2
Division of Cardiovascular Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
3
London Regional Research Centre, Robarts Research Institute, University of Western Ontario, London, ON, Canada.
4
Boston Heart Diagnostics, Framingham, MA, USA; Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
5
Boston Heart Diagnostics, Framingham, MA, USA.
6
Boston Heart Diagnostics, Framingham, MA, USA; Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. Electronic address: eschaefer@bostonheartdx.com.

Abstract

BACKGROUND:

Sitosterolemia is associated with increases in intestinal sterol absorption, low-density lipoprotein cholesterol (LDL-C), and cardiovascular disease risk.

OBJECTIVE:

We examined the relationship between hypercholesterolemia and sitosterolemia in a large population and report a new sitosterolemia case.

METHODS:

Plasma sterol concentrations were measured by gas chromatography/mass spectrometry, and LDL-C by direct assay.

RESULTS:

Of 207,926 subjects tested, 4.3% had LDL-C ≥190 mg/dL. Plasma β-sitosterol concentrations ≥8.0 mg/L (99th percentile) were found in 4.3% of these subjects vs 0.72% with LDL-C <130 mg/dL. Among all subjects, 0.050% had β-sitosterol levels ≥15.0 mg/L, consistent with sitosterolemia, while among those with LDL-C ≥190 mg/dL, 0.334% had this rare disorder. A 13-year-old boy with the highest LDL-C (679 mg/dL) of all subjects had planar xanthomas and a β-sitosterol level of 53.5 mg/L (normal <3.3 mg/L). He was a compound heterozygote for 2 ABCG8 mutations (p.N409D and an intron 11+2T>A splice site mutation). On a low-cholesterol and plant-sterol diet, his LDL-C decreased to 485 mg/dL (-29%) and β-sitosterol to 44.6 mg/L (-27%). On atorvastatin 20 mg/d, his LDL-C decreased to 299 mg/dL (-38%). With added ezetimibe 10 mg/d, his LDL-C normalized to 60 mg/dL (-80% further decrease); and his β-sitosterol decreased to 14.1 mg/L (-68% further decrease).

CONCLUSIONS:

Our data indicate that about 4% of subjects with LDL-C concentrations ≥190 mg/dL have plasma β-sitosterol concentrations above the 99th percentile and about 0.3% have concentrations consistent with sitosterolemia. Therefore, this diagnosis should be considered in such patients.

KEYWORDS:

ABCG5/G8 genes; Ezetimibe therapy; Hypercholesterolemia; LDL cholesterol; Sitosterolemia; Xanthomas

PMID:
29169939
DOI:
10.1016/j.jacl.2017.10.013
[Indexed for MEDLINE]

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