75372 20240116083604.0 doi 10.1016/j.jacl.2017.09.005 sideral 103589 ART-2017-103589 eng Lamiquiz-Moneo, I. Universidad de Zaragoza (orcid)0000-0001-8807-9187 ABCG5/G8 gene is associated with hypercholesterolemias without mutation in candidate genes and noncholesterol sterols 2017 Access copy available to the general public Unrestricted Context 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. info:eu-repo/semantics/openAccess by-nc-nd http://creativecommons.org/licenses/by-nc-nd/3.0/es/ 3.58 2017 PHARMACOLOGY & PHARMACY 61 / 260 = 0.235 2017 Q1 T1 1.654 2017 Cardiology and Cardiovascular Medicine 2017 Q1 Nutrition and Dietetics 2017 Q1 Internal Medicine 2017 Q1 Endocrinology, Diabetes and Metabolism 2017 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Baila-Rueda, L. Bea, A.M. Universidad de Zaragoza (orcid)0000-0001-6650-8294 Mateo-Gallego, R. (orcid)0000-0002-9647-0108 Pérez-Calahorra, S. (orcid)0000-0002-1894-1621 Marco-Benedí, V. Martín-Navarro, A. Ros, E. Cofán, M. Rodríguez-Rey, J.C. Pocovi, M. Cenarro, A. Civeira, F. Universidad de Zaragoza (orcid)0000-0001-7043-0952 1007 610 Universidad de Zaragoza Dpto. Medicina, Psiqu. y Derm. Area Medicina 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 11, 6 (2017), 1432-1440.e4 Journal of Clinical Lipidology Journal of Clinical Lipidology 1933-2874 151644 http://zaguan.unizar.es/record/75372/files/texto_completo.pdf Postprint 57378 http://zaguan.unizar.es/record/75372/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:75372 articulos driver 2024-01-16-08:32:21 ARTICLE