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Cited by 40Cholesterol and Lipid MetabolismLipoproteins and Cardiovascular HealthLipid metabolism and disorders

Familial Combined Hyperlipidemia Is Associated With Alterations in the Cholesterol Synthesis Pathway

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van Himbergen, Thomas M., Otokozawa, Seiko, Matthan, Nirupa R., Schaefer, Ernst J., Buchsbaum, Aaron, Ai, Masumi, van Tits, Lambertus J.H., de Graaf, Jacqueline +1 more·2010·Arteriosclerosis, Thrombosis, and Vascular Biology
DOI 10.1161/atvbaha.109.196550PMC PMC2813691
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Abstract

Objectives— Familial combined hyperlipidemia (FCH) is a common familial lipid disorder characterized by increases in plasma total cholesterol, triglyceride, and apolipoprotein B-100 levels. In light of prior metabolic and genetic research, our purpose was to ascertain whether FCH cases had significant abnormalities of plasma markers of cholesterol synthesis and absorption as compared to unaffected kindred members. Methods and Results— Plasma levels of squalene, desmosterol, and lathosterol (cholesterol synthesis markers) and campesterol, sitosterol, and cholestanol (cholesterol absorption markers) were measured by gas-liquid chromatography in 103 FCH patients and 240 normolipidemic relatives (NLR). Squalene, desmosterol, and lathosterol levels were 6% (0.078), 31%, ( P <0.001) and 51% ( P <0.001) higher in FCH as compared to NLR, and these differences were especially pronounced in women. An interaction with obesity was also noted for a subset of these markers. We did not observe any apparent differences for the cholesterol absorption markers among FCH patients and NLR. Conclusions— Our data indicate that both men and women with FCH have alterations in the cholesterol synthesis pathway, resulting in 51% higher levels of lathosterol (and additionally desmosterol in women). Plasma levels of the cholesterol precursor sterol squalene were only slightly increased (6%), suggesting enhanced conversion of squalene to lathosterol in this disorder.

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  • Individuals with low ApoB levels might have low lathosterol and desmosterol levels, as we detected in our subjects.

    “Individuals with familial combined hyperlipidemia-1 have elevated levels of PCSK9 [102], lathosterol, and desmosterol [103], so individuals with low ApoB levels might have low lathosterol and desmosterol levels, as we detected in our subjects.”

    From Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits (2021) · cites this paper as [103]

    The Results report elevated lathosterol in FCH patients and a correlation of both sterols with apoB. Desmosterol was significantly elevated in women with FCH, but not in men, so the unqualified statement that both sterols are elevated in individuals with FCH overstates the finding. The low-apoB statement is the citing authors’ inference, not a result established by this study. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Individuals with familial combined hyperlipidemia-1 have elevated levels of PCSK9, lathosterol, and desmosterol.

    “Individuals with familial combined hyperlipidemia-1 have elevated levels of PCSK9 [102], lathosterol, and desmosterol [103], so individuals with low ApoB levels might have low lathosterol and desmosterol levels, as we detected in our subjects.”

    From Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits (2021) · cites this paper as [103]

    The Results report elevated lathosterol in patients with familial combined hyperlipidemia (FCH) and elevated desmosterol overall, with the desmosterol increase pronounced in women but not statistically significant in men. The paper studies FCH generally and does not identify its participants as having the specified FCH-1 subtype. PCSK9 is attached to a different citation in the citing sentence. (LLM, conf=0.82)

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Authors
van Himbergen, T. M., Otokozawa, S., Matthan, N. R., Schaefer, E. J., Buchsbaum, A., Ai, M., van Tits, L. J. H., de Graaf, J., & Stalenhoef, A. F. H.
Affiliations
  • From the Lipid Metabolism (T.M.v.H., S.O., E.J.S., A.B., M.A.) and Cardiovascular Nutrition Laboratories (N.R.M.), Human Nutrition Research Center on Aging at Tufts University, Boston, Mass; and the Department of General Internal Medicine (L.J.H.v.T., J.d.G., A.F.H.S.), Radboud University Nijmegen Medical Center, The Netherlands.
  • Tufts University (US)
ORCID
Venue
Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2010-01
Volume
30
Issue
1
Pages
113-120
ISSN
  • 1079-5642 (ISSN-L)
  • 1524-4636
DOI
10.1161/atvbaha.109.196550
PMC
PMC2813691
OpenAlex
W2107481891
Cited by
40
References
2
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 3 · 2014: 6 · 2013: 2 · 2012: 4
FWCI
5.01
Type
journal article
Language
en
Open access
Locations
  • Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion, other-oa)
Funders
  • National Institutes of Health (53-3K-06, 5p50hl083813-05, PO50HL083813, 5t32dk007651-19)
  • National Heart, Lung, and Blood Institute (HL74753, R01HL074753, O50HL083813, R01HL060935, P50-HL083813)
  • National Institute of Diabetes and Digestive and Kidney Diseases (T32-DK-007651, DK07651)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords
familial combined hyperlipidemia, cholesterol biosynthesis, cholesterol absorption, squalene, desmosterol, lathosterol, campesterol, sitosterol, cholestanol, plasma sterols, obesity, sex differences, apolipoprotein B-100
MeSH terms
Adult, Aged, Cholesterol, Desmosterol, Cholestanol, Female, Humans, Hyperlipidemia, Familial Combined, Intestinal Absorption, Male, Middle Aged, Phytosterols, Sex Characteristics, Sitosterols, Squalene, Biomarkers

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