Diagnostic yield of sequencing familial hypercholesterolemia genes in individuals with primary hypercholesterolemia

Lamiquiz-Moneo, Itziar (Universidad de Zaragoza) ; Civeira, Fernando (Universidad de Zaragoza) ; Mateo-Gallego, Rocío (Universidad de Zaragoza) ; Laclaustra, Martín (Universidad de Zaragoza) ; Moreno-Franco, Belén (Universidad de Zaragoza) ; Tejedor, María Teresa (Universidad de Zaragoza) ; Palacios, Lourdes ; Martín, César ; Cenarro, Ana

Resumen: 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.

Idioma: Inglés

DOI: 10.1016/j.rec.2020.06.003

Año: 2021

Publicado en: Revista Española de Cardiología (English Edition) 74, 8 (2021), 664-673
ISSN: 1885-5857

Factor impacto CITESCORE: 2.4 - Medicine (Q3)

Factor impacto SCIMAGO: 0.385 - Medicine (miscellaneous) (Q3)

Financiación: info:eu-repo/grantAgreement/ES/DGA/B14-7R
Financiación: info:eu-repo/grantAgreement/ES/MINECO-ISCIII/CIBERCV
Financiación: info:eu-repo/grantAgreement/ES/MINECO/PI15-01983
Financiación: info:eu-repo/grantAgreement/ES/MINECO/PI18-01777

Tipo y forma: Artículo (PrePrint)

Área (Departamento): Área Enfermería (Dpto. Fisiatría y Enfermería)
Área (Departamento): Área Genética (Dpto. Anatom.,Embri.Genét.Ani.)
Área (Departamento): Area Anatom.Embriol.Humana (Dpto. Anatom.Histolog.Humanas)
Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)
Área (Departamento): Área Medic.Prevent.Salud Públ. (Dpto. Microb.Ped.Radio.Sal.Pú.)