Rendimiento diagnóstico de la secuenciación de genes de hipercolesterolemia familiar en sujetos con hipercolesterolemia primaria |
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Authors: | Itziar Lamiquiz-Moneo Fernando Civeira Rocío Mateo-Gallego Martín Laclaustra Belén Moreno-Franco María Teresa Tejedor Lourdes Palacios César Martín Ana Cenarro |
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Institution: | 1. Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Zaragoza, España;2. Departamento de Medicina, Psiquiatría y Dermatología, Universidad de Zaragoza, Zaragoza, España;3. Departamento de Fisiatría y Enfermería, Universidad de Zaragoza, Zaragoza, España;4. Fundación Agencia Aragonesa para la Investigación y el Desarrollo (ARAID), Zaragoza, España;5. Departamento de Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, Zaragoza, España;6. Unidad de Prevención Cardiovascular, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, España;7. Departamento de Anatomía, Embriología y Genética, Universidad de Zaragoza, Zaragoza, España;8. Departamento de I+D, Progenika Biopharma, a Grifols Company, Derio, Vizcaya, España;9. Instituto Biofisika (UPV/EHU, CSIC), Leioa, Vizcaya, España;10. Departamento de Bioquímica y Biología Molecular, Universidad del País Vasco, UPV/EHU, Bilbao, España;11. Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, España |
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Abstract: | Introduction and objectivesOur 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.MethodsUnrelated 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.ResultsOf 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).ConclusionsOur 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. |
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Keywords: | FH prevalence Mutation in candidate genes Lipoprotein(a) FH suspicion criteria AWHS"} {"#name":"keyword" "$":{"id":"kw0080"} "$$":[{"#name":"text" "$$":[{"#name":"italic" "_":"Aragon Workers’ Health Study"} {"#name":"__text__" "_":" (Estudio de Salud de los Trabajadores de Aragón) cLDL"} {"#name":"keyword" "$":{"id":"kw0090"} "$$":[{"#name":"text" "_":"colesterol unido a las lipoproteínas de baja densidad EC"} {"#name":"keyword" "$":{"id":"kw0100"} "$$":[{"#name":"text" "_":"enfermedad coronaria HF"} {"#name":"keyword" "$":{"id":"kw0110"} "$$":[{"#name":"text" "_":"hipercolesterolemia familiar |
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