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Title: Homozygous familial hypercholesterolemia in Spain prevalence and phenotype-genotype relationship
Authors: Civeira Murillo, Fernando
Stef, Marianne A.
Pérez Calahorra, Sofía
Almagro Múgica, Fátima
Plana Gil, Nuria
Sáenz Aranzubía, Pedro Enrique
Mosquera Lozano, Daniel
Soler i Ferrer, Cristina
Fuentes Jiménez, Francisco José
Brito Casillas, Yeray 
Real Collado, José Tomás
Blanco Vaca, Francisco 
Ascaso Gimilio, Juan Francisco
Pocovi Mieras, Miguel
Sánchez Hernández, Rosa María 
Novoa Mogollón, Francisco 
UNESCO Clasification: 32 Ciencias médicas
3207 Patología
320704 Patología cardiovascular
Keywords: Alleles
Issue Date: 2016
Publisher: 1942-325X
Journal: Circulation. Cardiovascular genetics 
Abstract: Background-Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and extremely high risk of premature atherosclerotic cardiovascular disease. HoFH is caused by mutations in several genes, including LDL receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and LDL protein receptor adaptor 1 (LDLRAP1). No epidemiological studies have assessed HoFH prevalence or the clinical and molecular characteristics of this condition. Here, we aimed to characterize HoFH in Spain. Methods and Results-Data were collected from the Spanish Dyslipidemia Registry of the Spanish Atherosclerosis Society and from all molecular diagnoses performed for familial hypercholesterolemia in Spain between 1996 and 2015 (n=16 751). Clinical data included baseline lipid levels and atherosclerotic cardiovascular disease events. A total of 97 subjects were identified as having HoFH-of whom, 47 were true homozygous (1 for APOB, 5 for LDLRAP1, and 41 for LDLR), 45 compound heterozygous for LDLR, 3 double heterozygous for LDLR and PSCK9, and 2 double heterozygous for LDLR and APOB. No PSCK9 homozygous cases were identified. Two variants in LDLR were identified in 4.8% of the molecular studies. Over 50% of patients did not meet the classical HoFH diagnosis criteria. The estimated HoFH prevalence was 1: 450 000. Compared with compound heterozygous cases, true homozygous cases showed more aggressive phenotypes with higher LDL-C and more atherosclerotic cardiovascular disease events. Conclusions-HoFH frequency in Spain was higher than expected. Clinical criteria would underestimate the actual prevalence of individuals with genetic HoFH, highlighting the importance of genetic analysis to improve familial hypercholesterolemia diagnosis accuracy.
ISSN: 1942-325X
DOI: 10.1161/CIRCGENETICS.116.001545
Source: Circulation. Cardiovascular Genetics [ISSN 1942-325X], v. 9 (6), p. 504-510
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