1. Homozygous Familial Hypercholesterolemia in Spain Prevalence and Phenotype-Genotype Relationship
- Author
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Núria Plana, Juan F. Ascaso, José T. Real, Sofía Pérez-Calahorra, Rosa M. Sánchez-Hernández, Marianne Stef, Fátima Almagro, Yeray Brito-Casillas, Francisco Blanco-Vaca, Francisco Fuentes, Daniel Mosquera, Miguel Pocovi, Cristina Soler, Francisco J Nóvoa, Fernando Civeira, Pedro Sáenz-Aranzubía, [Sanchez-Hernandez, Rosa M.] Complejo Hosp Univ Insular Materno Infantil Gran, Secc Endocrinol & Nutr, Las Palmas Gran Canaria, Spain, [Novoa, Francisco J.] Complejo Hosp Univ Insular Materno Infantil Gran, Secc Endocrinol & Nutr, Las Palmas Gran Canaria, Spain, [Brito-Casillas, Yeray] Complejo Hosp Univ Insular Materno Infantil Gran, Secc Endocrinol & Nutr, Las Palmas Gran Canaria, Spain, [Sanchez-Hernandez, Rosa M.] Univ Las Palmas Gran Canaria, IUIBS, Las Palmas Gran Canaria, Spain, [Novoa, Francisco J.] Univ Las Palmas Gran Canaria, IUIBS, Las Palmas Gran Canaria, Spain, [Brito-Casillas, Yeray] Univ Las Palmas Gran Canaria, IUIBS, Las Palmas Gran Canaria, Spain, [Civeira, Fernando] Univ Zaragoza, Inst Invest Sanitaria IIS Aragon, Hosp Univ Miguel Servet, Unidad Lipidos,RIC, Zaragoza, Spain, [Perez-Calahorra, Sofia] Univ Zaragoza, Inst Invest Sanitaria IIS Aragon, Hosp Univ Miguel Servet, Unidad Lipidos,RIC, Zaragoza, Spain, [Stef, Marianne] Progenika Biopharma SA, Derio, Vizcaya, Spain, [Almagro, Fatima] Hosp Donostia San Sebastian, Unidad Lipidos, Guipuzcoa, Spain, [Plana, Nuria] Univ Rovira & Virgili, Hosp Univ St Joan, Unidad Invest Lipidos & Arteriosclerosis, Unidad Med Vasc & Metab,IISPV, Tarragona, Spain, [Saenz-Aranzubia, Pedro] Hosp Merida, Unidad Lipidos, Merida, Spain, [Mosquera, Daniel] Hosp San Pedro & San Millan, Unidad Lipidos, Logrono, Spain, [Soler, Cristina] Hosp Santa Caterina Salt, Unidad Lipidos & Arteriosclerosis, Girona, Spain, [Fuentes, Francisco J.] Univ Cordoba, Hosp Univ Reina Sofia, Inst Maimonedes Invest Biomed Cordoba IMIBIC, Cordoba, Spain, [Fuentes, Francisco J.] Inst Salud Carlos III, Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Madrid, Spain, [Real, Jose T.] Univ Valencia, Hosp Clin Univ Valencia, CIBERDEM, Serv Endocrinol & Nutr, Valencia, Spain, [Ascaso, Juan F.] Univ Valencia, Hosp Clin Univ Valencia, CIBERDEM, Serv Endocrinol & Nutr, Valencia, Spain, [Blanco-Vaca, Francisco] Univ Autonoma Barcelona, Dept Bioquim & Biol Mol, Inst Invest Biomed St Pau IIB, Barcelona, Spain, [Blanco-Vaca, Francisco] Ctr Invest Biomed Red Diabet & Enfermedades Metab, Barcelona, Spain, [Pocovi, Miguel] Univ Zaragoza, Fac Ciencias, Dept Bioquim & Biol Mol & Celular, Zaragoza, Spain, [Pocovi, Miguel] IIS Aragon, Zaragoza, Spain, Spanish Ministry of Economy and Competitiveness, Marato TV3 foundation, and Red de Investigacion Cardiovascular (RIC)
- Subjects
Male ,0301 basic medicine ,Oncology ,Ldl receptor gene ,Apolipoprotein B ,Lipid-lowering therapy ,Familial hypercholesterolemia ,030204 cardiovascular system & hematology ,Compound heterozygosity ,0302 clinical medicine ,Autosomal-dominant hypercholesterolemia ,Risk Factors ,Epidemiology ,Prevalence ,Disease ,Registries ,Genetics (clinical) ,Molecular Epidemiology ,biology ,hypercholesterolemia ,Homozygote ,Double-blind ,Middle Aged ,Phenotype ,Cardiovascular Diseases ,Apolipoprotein B-100 ,alleles ,Female ,lipids (amino acids, peptides, and proteins) ,Proprotein Convertase 9 ,Cardiology and Cardiovascular Medicine ,Mutations ,Adult ,Genetic Markers ,Heterozygote ,medicine.medical_specialty ,Inhibitor ,Adolescent ,Placebo-controlled trial ,Hyperlipoproteinemia Type II ,lipids ,Young Adult ,03 medical and health sciences ,Internal medicine ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,Adaptor Proteins, Signal Transducing ,Recessive hypercholesterolemia ,PCSK9 ,registries ,Cholesterol, LDL ,Apolipoprotein-b ,medicine.disease ,030104 developmental biology ,Endocrinology ,Receptors, LDL ,Spain ,Mutation ,LDL receptor ,biology.protein ,mutation ,Dyslipidemia - 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.
- Published
- 2016
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