Ezetimibe Reduces Plant Sterol Accumulation and Favorably Increases Platelet Count in Sitosterolemia - 17/10/14

Doi : 10.1016/j.jpeds.2014.08.069

Rgia A. Othman, MS ^1,², Semone B. Myrie, PhD ^1,², David Mymin, MD ³, Louise S. Merkens, PhD ⁴, Jean-Baptiste Roullet, PhD ⁴, Robert D. Steiner, MD ^4,^5,⁶, Peter J.H. Jones, PhD ^1,^2,^⁎
¹ Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
² Richardson Center for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada
³ Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
⁴ Pediatrics, Institute on Development and Disability/Doernbecher Children's Hospital, Oregon Health and Science University, Portland, OR
⁵ Molecular and Medical Genetics, Institute on Development and Disability/Doernbecher Children's Hospital, Oregon Health and Science University, Portland, OR
⁶ Marshfield Clinic Research Foundation, Marshfield, WI and the University of Wisconsin, Madison, WI

^∗Reprint requests: Peter J. H. Jones, PhD, Richardson Center for Functional Foods and Nutraceuticals, University of Manitoba, 196 Innovation Dr, Winnipeg, MB R3T 6C5, Canada.

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Friday 17 October 2014

Abstract

Objective

To assess if ezetimibe (EZE), a sterol-absorption inhibitor, improves platelet (PLT) count and size relative to its effect on plasma plant sterol (PS) in patients with sitosterolemia (STSL).

Study design

Patients with STSL (5 males, 3 females, 16-56 years of age) receiving EZE intervention as part of their routine care participated in this study. EZE was discontinued for 14 weeks (off) and then resumed for another 14 weeks (on). Hematology variables along with plasma and red blood cells (RBC) PS and total cholesterol (TC) levels were measured at the end of each phase.

Results

EZE increased PLT count (23% ± 9%) and decreased mean PLT volume (MPV; 10% ± 3%, all P < .05). In patients off EZE, PLT counts inversely correlated (r = −0.96 and r = −0.91, all P < .01) with plasma and RBC PS to TC ratio (PS/TC), and MPV positively correlated (r = 0.91, P = .03 and r = 0.93, P = .02) with plasma and RBC PS/TC. EZE reduced plasma and RBC sitosterol (−35% ± 4% and −28% ± 3%), total PS (−37% ± 4% and −28% ± 3%, all P < .0001) levels, and PS/TC (−27% ± 4% and −28% ± 4%, P < .01).

Conclusions

EZE reduces plasma and RBC PS levels, while increasing PLT count and decreasing MPV, and thereby may reduce the risk for bleeding in STSL. Plasma PS levels and ABCG5/ABCG8 genes should be analyzed in patients with unexplained hematologic abnormalities.

Le texte complet de cet article est disponible en PDF.

Keyword : ABC, EZE, Hb, LDL, MCHC, MPV, PLT, PS, PS/TC, RBC, RDW, STSL, TC

Plan

Supported by the Canadian Institutes of Health Research (MOP12339). The Sterol and Isoprenoid Research (STAIR; U54HD061939) Consortium is a part of the National Institutes of Health (NIH) Rare Diseases Clinical Research Network, supported through collaboration between the NIH Office of Rare Diseases Research at the National Center for Advancing Translational Science, and National Institute of Child Health and Human Development. R.O. was supported by the Libyan Scholarship Program and the Manitoba Health Research Council Graduate Student Fellowship. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors declare no conflicts of interest.

Registered with www.ClinicalTrials.gov: NCT01584206.