Author:
Sánchez-Hernández Rosa M.,Civeira Fernando,Stef Marianne,Perez-Calahorra Sofía,Almagro Fátima,Plana Nuria,Novoa Francisco J.,Sáenz-Aranzubía Pedro,Mosquera Daniel,Soler Cristina,Fuentes Francisco J.,Brito-Casillas Yeray,Real Jose T.,Blanco-Vaca Francisco,Ascaso Juan F.,Pocovi Miguel
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Genetics (clinical),Cardiology and Cardiovascular Medicine,Genetics
Cited by
62 articles.
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