000076017 001__ 76017 000076017 005__ 20240122154813.0 000076017 0247_ $$2doi$$a10.1016/j.jsbmb.2016.10.003 000076017 0248_ $$2sideral$$a99024 000076017 037__ $$aART-2017-99024 000076017 041__ $$aeng 000076017 100__ $$aBaila-Rueda, L. 000076017 245__ $$aBile acid synthesis precursors in subjects with genetic hypercholesterolemia negative for LDLR/APOB/PCSK9/APOE mutations. Association with lipids and carotid atherosclerosis 000076017 260__ $$c2017 000076017 5060_ $$aAccess copy available to the general public$$fUnrestricted 000076017 5203_ $$aSome oxysterols are precursors of bile acid synthesis and play an important role in cholesterol homeostasis. However, if they are involved in the pathogeny of genetic hypercholesterolemia has not been previously explored. We have studied non-cholesterol sterol markers of cholesterol synthesis (lanosterol and desmosterol) and oxysterols (7a-hydroxy-4-cholesten-3-one, 24S-hydroxycholesterol and 27-hydroxycholesterol) in 200 affected subjects with primary hypercholesterolemia of genetic origin, negative for mutations in LDLR, APOB, PCSK9 and APOE genes (non-FH GH) and 100 normolipemic controls. All studied oxysterols and cholesterol synthesis markers were significantly higher in affected subjects than controls (P < 0.001). Ratios of oxysterols to total cholesterol were higher in non-FH GH than in controls, although only 24S-hydroxycholesterol showed statistical significance (P < 0.001). Cholesterol synthesis markers had a positive correlation with BMI, triglycerides, cholesterol and apoB in control population. However, these correlations disappeared in non-FH GH with the exception of a weak positive correlation for non-HDL cholesterol and apoB. The same pattern was observed for oxysterols with high positive correlation in controls and absence of correlation for non-FH GH, except non-HDL cholesterol for 24S-hydroxycholesterol and 27-hydroxycholesterol and apoB for 27-hydroxycholesterol. All non-cholesterol sterols had positive correlation among them in patients and in controls. A total of 65 (32.5%) and 35 (17.5%) affected subjects presented values of oxysterols ratios to total cholesterol above the 95th percentile of the normal distribution (24S-hydroxycholesterol and 27-hydroxycholesterol, respectively). Those patients with the highest levels of 24S-hydroxycholesterol associated an increase in the carotid intima media thickness. These results suggest that bile acid metabolism is affected in some patients with primary hypercholesterolemia of genetic origin, negative for mutations in the candidate genes, and may confer a higher cardiovascular risk. Our results confirm that cholesterol synthesis overproduction is a primary defect in non-HF GH and suggest that subjects with non-FH GH show high levels of oxysterols in response to hepatic overproduction of cholesterol. 000076017 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/RD12-0042-0055$$9info:eu-repo/grantAgreement/ES/MINECO/PI12-01087 000076017 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/ 000076017 590__ $$a4.095$$b2017 000076017 591__ $$aENDOCRINOLOGY & METABOLISM$$b32 / 141 = 0.227$$c2017$$dQ1$$eT1 000076017 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b69 / 292 = 0.236$$c2017$$dQ1$$eT1 000076017 592__ $$a1.431$$b2017 000076017 593__ $$aEndocrinology, Diabetes and Metabolism$$c2017$$dQ1 000076017 593__ $$aClinical Biochemistry$$c2017$$dQ1 000076017 593__ $$aBiochemistry$$c2017$$dQ1 000076017 593__ $$aMolecular Biology$$c2017$$dQ2 000076017 593__ $$aMolecular Medicine$$c2017$$dQ2 000076017 593__ $$aEndocrinology$$c2017$$dQ2 000076017 593__ $$aCell Biology$$c2017$$dQ2 000076017 655_4 $$ainfo:eu-repo/semantics/review$$vinfo:eu-repo/semantics/acceptedVersion 000076017 700__ $$aCenarro, A. 000076017 700__ $$0(orcid)0000-0002-9647-0108$$aLamiquiz-Moneo, I. 000076017 700__ $$0(orcid)0000-0001-6650-8294$$aMateo-Gallego, R.$$uUniversidad de Zaragoza 000076017 700__ $$aBea, A.M. 000076017 700__ $$0(orcid)0000-0002-1894-1621$$aPerez-Calahorra, S. 000076017 700__ $$aMarco-Benedi, V. 000076017 700__ $$0(orcid)0000-0001-7043-0952$$aCiveira, F.$$uUniversidad de Zaragoza 000076017 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina 000076017 773__ $$g169 (2017), 226-233$$pJ. steroid biochem. mol. biol.$$tJOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY$$x0960-0760 000076017 8564_ $$s264112$$uhttps://zaguan.unizar.es/record/76017/files/texto_completo.pdf$$yPostprint 000076017 8564_ $$s92490$$uhttps://zaguan.unizar.es/record/76017/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint 000076017 909CO $$ooai:zaguan.unizar.es:76017$$particulos$$pdriver 000076017 951__ $$a2024-01-22-15:31:11 000076017 980__ $$aARTICLE