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

Author:

van Himbergen Thomas M.1,Otokozawa Seiko1,Matthan Nirupa R.1,Schaefer Ernst J.1,Buchsbaum Aaron1,Ai Masumi1,van Tits Lambertus J.H.1,de Graaf Jacqueline1,Stalenhoef Anton F.H.1

Affiliation:

1. 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.

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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