000075372 001__ 75372
000075372 005__ 20240116083604.0
000075372 0247_ $$2doi$$a10.1016/j.jacl.2017.09.005
000075372 0248_ $$2sideral$$a103589
000075372 037__ $$aART-2017-103589
000075372 041__ $$aeng
000075372 100__ $$0(orcid)0000-0001-8807-9187$$aLamiquiz-Moneo, I.$$uUniversidad de Zaragoza
000075372 245__ $$aABCG5/G8 gene is associated with hypercholesterolemias without mutation in candidate genes and noncholesterol sterols
000075372 260__ $$c2017
000075372 5060_ $$aAccess copy available to the general public$$fUnrestricted
000075372 5203_ $$aContext Approximately 20% to 40% of clinically defined familial hypercholesterolemia (FH) cases do not show a causative mutation in candidate genes (mutation-negative FH), and some of them may have a polygenic origin. Objective The aim of this work was to study the prevalence of ABCG5/G8 genetic variants in mutation-negative FH, as defects in these genes relate to intestinal hyperabsorption of cholesterol and thus ABCG5/G8 variants could explain in part the mechanism of hypercholesterolemia. Design, setting, and patients We sequenced the ABCG5/G8 genes in 214 mutation-negative FH and 97 controls. Surrogate markers of cholesterol absorption (5a-cholestanol, ß-sitosterol, campesterol, stigmasterol, and sitostanol) were quantified by high-performance liquid chromatography–tandem mass spectrometry in both studied groups. Results We found 8 mutation-negative FH patients (3.73%) with a pathogenic mutation in ABCG5/G8 genes. We observed significantly higher concentration of surrogate markers of cholesterol absorption in mutation-negative FH than in controls. In addition, we found significantly higher concentrations of cholesterol absorption markers in mutation-negative FH with ABCG5/G8 defects than in mutation-negative, ABCG5/G8-negative FH. A gene score reflecting the number of common single nucleotide variants associated with hypercholesterolemia was significantly higher in cases than in controls (P =.032). Subjects with a gene score above the mean had significantly higher 5a-cholestanol and stigmasterol than those with a lower gene score. Conclusions Mutation-negative FH subjects accumulate an excess of rare and common gene variations in ABCG5/G8 genes. This variation is associated with increased intestinal absorption of cholesterol, as determined by surrogate makers, suggesting that these loci contribute to hypercholesterolemia by enhancing intestinal cholesterol absorption.
000075372 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000075372 590__ $$a3.58$$b2017
000075372 591__ $$aPHARMACOLOGY & PHARMACY$$b61 / 260 = 0.235$$c2017$$dQ1$$eT1
000075372 592__ $$a1.654$$b2017
000075372 593__ $$aCardiology and Cardiovascular Medicine$$c2017$$dQ1
000075372 593__ $$aNutrition and Dietetics$$c2017$$dQ1
000075372 593__ $$aInternal Medicine$$c2017$$dQ1
000075372 593__ $$aEndocrinology, Diabetes and Metabolism$$c2017$$dQ1
000075372 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000075372 700__ $$aBaila-Rueda, L.
000075372 700__ $$0(orcid)0000-0001-6650-8294$$aBea, A.M.$$uUniversidad de Zaragoza
000075372 700__ $$0(orcid)0000-0002-9647-0108$$aMateo-Gallego, R.
000075372 700__ $$0(orcid)0000-0002-1894-1621$$aPérez-Calahorra, S.
000075372 700__ $$aMarco-Benedí, V.
000075372 700__ $$aMartín-Navarro, A.
000075372 700__ $$aRos, E.
000075372 700__ $$aCofán, M.
000075372 700__ $$aRodríguez-Rey, J.C.
000075372 700__ $$aPocovi, M.
000075372 700__ $$aCenarro, A.
000075372 700__ $$0(orcid)0000-0001-7043-0952$$aCiveira, F.$$uUniversidad de Zaragoza
000075372 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000075372 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000075372 773__ $$g11, 6 (2017), 1432-1440.e4$$pJournal of Clinical Lipidology$$tJournal of Clinical Lipidology$$x1933-2874
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000075372 951__ $$a2024-01-16-08:32:21
000075372 980__ $$aARTICLE