129442 20231219145827.0 doi 10.1016/j.jacl.2016.09.011 sideral 97499 ART-2016-97499 eng Jarauta, E. (orcid)0000-0001-6650-8294 Lipid phenotype and heritage pattern in families with genetic hypercholesterolemia not related to LDLR, APOB, PCSK9, or APOE 2016 Background: A substantial proportion of individuals clinically diagnosed as familial hypercholesterolemia (FH) do not carry pathogenic mutations in candidate genes. Whether in them the high cholesterol trait is transmitted monogenically has not been studied. Objectives: We assessed the inheritance pattern, penetrance, and expression of high low-density lipoprotein (LDL)-cholesterol (LDLc) in families with genetic hypercholesterolemia (GH) without known causative mutations (non-FH-GH). Methods: The study included probands with a clinical diagnosis of FH and their families attending 2 lipid clinics in Spain. Inclusion criteria for probands were LDLc >95th percentile, triglycerides 90th percentile, >5 points in the Dutch Lipid Clinic Network criteria score, and absence of mutations in LDLR, APOB, PCSK9 or APOE. Eleven FH families with a LDLR mutation were also examined for comparison. Results: We analyzed 49 non-FH-GH probands and 277 first-and second-degree relatives. LDLc was >90th percentile in 37.8% of blood relatives, at concentrations similar to those of probands. LDLc had a normal distribution in non-FH-GH families, in contrast with a bimodal distribution in FH families. When a dominant model was tested, family-based association tests gave much lower heritability values for total cholesterol and LDLc in non-FH-GH (0.39 and 0.32, respectively) than in FH (0.78 and 0.61, respectively). Conclusions: Non-FH-GH families have a milder lipid phenotype than genetically defined FH. The heritage pattern of LDLc in non-FH-GH does not fit with a monogenic disorder. Our findings support the concept that most non-FH-GHs are polygenic hypercholesterolemias. Access copy available to the general public Unrestricted info:eu-repo/grantAgreement/ES/ISCIII/RD12-0042-0055 info:eu-repo/grantAgreement/ES/MINECO/PI12-01087 info:eu-repo/grantAgreement/ES/MINECO/PI12-01321 info:eu-repo/grantAgreement/ES/MINECO/PI12-01703 info:eu-repo/semantics/openAccess by-nc-nd http://creativecommons.org/licenses/by-nc-nd/3.0/es/ 5.812 2016 PHARMACOLOGY & PHARMACY 17 / 256 = 0.066 2016 Q1 T1 2.177 2016 Cardiology and Cardiovascular Medicine 2016 Q1 Nutrition and Dietetics 2016 Q1 Internal Medicine 2016 Q1 Endocrinology, Diabetes and Metabolism 2016 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Pérez-Ruiz, M. R. Pérez-Calahorra, S. Universidad de Zaragoza (orcid)0000-0001-9142-0737 Mateo-Gallego, R. (orcid)0000-0002-1894-1621 Cenarro, A. Cofán, M. Ros, E. Civeira, F. Universidad de Zaragoza (orcid)0000-0001-7043-0952 Tejedor, M. T. Universidad de Zaragoza (orcid)0000-0001-5026-5144 1001 420 Universidad de Zaragoza Dpto. Anatom.,Embri.Genét.Ani. Área Genética 1007 610 Universidad de Zaragoza Dpto. Medicina, Psiqu. y Derm. Area Medicina 10, 6 (2016), 1397-1405.e2 Journal of Clinical Lipidology Journal of Clinical Lipidology 1933-2874 642485 http://zaguan.unizar.es/record/129442/files/texto_completo.pdf Postprint 858390 http://zaguan.unizar.es/record/129442/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:129442 articulos driver 2023-12-19-13:58:42 ARTICLE