148185 20250114175434.0 doi 10.1016/j.rec.2020.06.003 sideral 131159 ART-2021-131159 eng Lamiquiz-Moneo, Itziar Universidad de Zaragoza (orcid)0000-0002-9647-0108 Diagnostic yield of sequencing familial hypercholesterolemia genes in individuals with primary hypercholesterolemia 2021 Introduction and objectives: Our objective was to approximate the prevalence of mutations in candidate genes for familial hypercholesterolemia (FH) in a middle-aged Spanish population and to establish the predictive value of criteria for clinical suspicion in the detection of causative mutations. Methods: Unrelated individuals aged = 18 years from the Aragon Workers’ Health Study (AWHS) with high low-density lipoprotein cholesterol (LDL-C) and clinical suspicion of FH (participants with LDL-C concentrations above the 95th percentile, participants with premature cardiovascular disease and/or participants with high LDL-C [130 mg/dL] under statin therapy), assuming that any participant with FH exhibits at leats 1 trait, were selected and the LDLR, APOB, PCSK9, APOE, STAP1 and LDLRAP1 genes were sequenced by next generation sequencing technology. Results: Of 5400 individuals from the AWHS, 4514 had complete data on lipid levels and lipid-lowering drugs, 255 participants (5.65%) met the criteria for suspicion of FH, 24 of them (9.41%) were diagnosed with hyperlipoproteinemia(a), and 16 (6.27% of those sequenced) were found to carry causative mutations in candidate genes: 12 participants carried 11 different pathogenic LDLR alleles and 4 participants carried 1 pathogenic mutation in PCSK9. LDL-C concentrations > 220 mg/dL and LDL-C > 130 mg/dL despite statin therapy showed the strongest association with the presence of mutations (P = .011). Conclusions: Our results show that the prevalence of FH in Spain is 1:282 and suggest that the combination of high untreated LDL-C and high levels of LDL-C despite statin therapy are the best predictors of a positive FH genetic test. Access copy available to the general public Unrestricted info:eu-repo/grantAgreement/ES/DGA/B14-7R info:eu-repo/grantAgreement/ES/MINECO-ISCIII/CIBERCV info:eu-repo/grantAgreement/ES/MINECO/PI15-01983 info:eu-repo/grantAgreement/ES/MINECO/PI18-01777 info:eu-repo/semantics/openAccess by-nc-nd http://creativecommons.org/licenses/by-nc-nd/3.0/es/ 0.385 2021 Medicine (miscellaneous) 2021 Q3 2.4 2021 info:eu-repo/semantics/article info:eu-repo/semantics/submittedVersion Civeira, Fernando Universidad de Zaragoza (orcid)0000-0001-7043-0952 Mateo-Gallego, Rocío Universidad de Zaragoza (orcid)0000-0001-6650-8294 Laclaustra, Martín Universidad de Zaragoza (orcid)0000-0003-3963-0846 Moreno-Franco, Belén Universidad de Zaragoza (orcid)0000-0003-0604-5042 Tejedor, María Teresa Universidad de Zaragoza (orcid)0000-0001-5026-5144 Palacios, Lourdes Martín, César Cenarro, Ana 1006 255 Universidad de Zaragoza Dpto. Fisiatría y Enfermería Área Enfermería 1001 420 Universidad de Zaragoza Dpto. Anatom.,Embri.Genét.Ani. Área Genética 1003 027 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Anatom.Embriol.Humana 1007 610 Universidad de Zaragoza Dpto. Medicina, Psiqu. y Derm. Area Medicina 1011 615 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Medic.Prevent.Salud Públ. 74, 8 (2021), 664-673 Revista Española de Cardiología (English Edition) 1885-5857 369525 http://zaguan.unizar.es/record/148185/files/texto_completo.pdf Preprint 2560741 http://zaguan.unizar.es/record/148185/files/texto_completo.jpg?subformat=icon icon Preprint oai:zaguan.unizar.es:148185 articulos driver 2025-01-14-15:49:04 ARTICLE