000129442 001__ 129442
000129442 005__ 20231219145827.0
000129442 0247_ $$2doi$$a10.1016/j.jacl.2016.09.011
000129442 0248_ $$2sideral$$a97499
000129442 037__ $$aART-2016-97499
000129442 041__ $$aeng
000129442 100__ $$0(orcid)0000-0001-6650-8294$$aJarauta, E.
000129442 245__ $$aLipid phenotype and heritage pattern in families with genetic hypercholesterolemia not related to LDLR, APOB, PCSK9, or APOE
000129442 260__ $$c2016
000129442 5060_ $$aAccess copy available to the general public$$fUnrestricted
000129442 5203_ $$aBackground: A substantial proportion of individuals clinically diagnosed as familial hypercholesterolemia (FH) do not carry pathogenic mutations in candidate genes. Whether in them the high cholesterol trait is transmitted monogenically has not been studied. Objectives: We assessed the inheritance pattern, penetrance, and expression of high low-density lipoprotein (LDL)-cholesterol (LDLc) in families with genetic hypercholesterolemia (GH) without known causative mutations (non-FH-GH). Methods: The study included probands with a clinical diagnosis of FH and their families attending 2 lipid clinics in Spain. Inclusion criteria for probands were LDLc >95th percentile, triglycerides 90th percentile, >5 points in the Dutch Lipid Clinic Network criteria score, and absence of mutations in LDLR, APOB, PCSK9 or APOE. Eleven FH families with a LDLR mutation were also examined for comparison. Results: We analyzed 49 non-FH-GH probands and 277 first-and second-degree relatives. LDLc was >90th percentile in 37.8% of blood relatives, at concentrations similar to those of probands. LDLc had a normal distribution in non-FH-GH families, in contrast with a bimodal distribution in FH families. When a dominant model was tested, family-based association tests gave much lower heritability values for total cholesterol and LDLc in non-FH-GH (0.39 and 0.32, respectively) than in FH (0.78 and 0.61, respectively). Conclusions: Non-FH-GH families have a milder lipid phenotype than genetically defined FH. The heritage pattern of LDLc in non-FH-GH does not fit with a monogenic disorder. Our findings support the concept that most non-FH-GHs are polygenic hypercholesterolemias.
000129442 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/RD12-0042-0055$$9info:eu-repo/grantAgreement/ES/MINECO/PI12-01087$$9info:eu-repo/grantAgreement/ES/MINECO/PI12-01321$$9info:eu-repo/grantAgreement/ES/MINECO/PI12-01703
000129442 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000129442 590__ $$a5.812$$b2016
000129442 591__ $$aPHARMACOLOGY & PHARMACY$$b17 / 256 = 0.066$$c2016$$dQ1$$eT1
000129442 592__ $$a2.177$$b2016
000129442 593__ $$aCardiology and Cardiovascular Medicine$$c2016$$dQ1
000129442 593__ $$aNutrition and Dietetics$$c2016$$dQ1
000129442 593__ $$aInternal Medicine$$c2016$$dQ1
000129442 593__ $$aEndocrinology, Diabetes and Metabolism$$c2016$$dQ1
000129442 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000129442 700__ $$aPérez-Ruiz, M. R.
000129442 700__ $$0(orcid)0000-0001-9142-0737$$aPérez-Calahorra, S.$$uUniversidad de Zaragoza
000129442 700__ $$0(orcid)0000-0002-1894-1621$$aMateo-Gallego, R.
000129442 700__ $$aCenarro, A.
000129442 700__ $$aCofán, M.
000129442 700__ $$aRos, E.
000129442 700__ $$0(orcid)0000-0001-7043-0952$$aCiveira, F.$$uUniversidad de Zaragoza
000129442 700__ $$0(orcid)0000-0001-5026-5144$$aTejedor, M. T.$$uUniversidad de Zaragoza
000129442 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Genética
000129442 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000129442 773__ $$g10, 6 (2016), 1397-1405.e2$$pJournal of Clinical Lipidology$$tJournal of Clinical Lipidology$$x1933-2874
000129442 8564_ $$s642485$$uhttps://zaguan.unizar.es/record/129442/files/texto_completo.pdf$$yPostprint
000129442 8564_ $$s858390$$uhttps://zaguan.unizar.es/record/129442/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000129442 909CO $$ooai:zaguan.unizar.es:129442$$particulos$$pdriver
000129442 951__ $$a2023-12-19-13:58:42
000129442 980__ $$aARTICLE