A carregar...
Publicação
Estudo Português de Hipercolesterolemia Familiar
Orientador(es)
Resumo(s)
A Hipercolesterolemia Familiar (FH) é uma doença genética associada a
um elevado risco cardiovascular. Doentes com FH possuem valores muito
elevados de colesterol no plasma, desde o nascimento. Até à data 3 genes
foram associados à FH: LDLR (85-90%), APOB (5-8%) e PCSK9 (1-2%). Em
1999 foi estabelecido, no Instituto Nacional de Saúde Doutor Ricardo Jorge,
o Estudo Português de Hipercolesterolemia Familiar (EPHF). Este estudo de
investigação tem como objetivo principal identificar a causa genética da
dislipidemia em doentes com critérios clínicos de FH. O EPHF identificou
molecularmente 718 doentes heterozigotos com uma variante patogénica
ou provavelmente patogénica (segundo as diretrizes da ACMG) num dos 3
genes associados à FH. Adicionalmente, 90 indivíduos possuem uma das
35 variantes de significado incerto cuja patogenicidade necessita de ser
avaliada através de estudos funcionais. Foram também identificados 10 homozigotos
(3 homozigotos verdadeiros e 7 heterozigotos compostos), com
variantes patogénicas nos genes LDLR e PCSK9. O EPHF conseguiu identificar
3,8% dos portugueses que se calcula terem FH, colocando Portugal
entre os dez países com mais doentes identificados. O risco cardiovascular
dos doentes com FH é determinado pelos valores elevados de colesterol
que os doentes apresentam desde o nascimento, mas também pela patogenicidade
da variante identificada. A identificação precoce dos doentes
com FH, através do diagnóstico genético, permite ao clínico implementar
medidas terapêuticas adequadas e mais agressivas, de modo a diminuir o
risco cardiovascular inerente a estes doentes.
Familial Hypercholesterolemia (FH) is a genetic disorder associated with a high cardiovascular risk. Patients with FH have very high plasma cholesterol values since birth. Until now three genes have been associated to FH: LDLR (85-90%), APOB (5-8%) and PCSK9 (1-2%). In 1999 the Portuguese FH (PFHS) Study was established at the National Institute of Health. This study aims to identify the genetic cause of dyslipidemia in patients with clinical diagnosis of FH. The Portuguese FH Study genetically identified 718 heterozygous patients with a pathogenic or probably pathogenic variant (according to ACMG guidelines) in one of the 3 genes associated to FH. In addition, 90 individuals have one of 35 variants of uncertain significance whose pathogenicity needs to be assessed through functional studies. Ten homozygotes (3 true homozygotes and 7 heterozygous compounds) were also identified, with pathogenic variants in the LDLR and PCSK9 genes. The PFHS was able to identify 3.8% of the Portuguese that are estimated to have FH, placing Portugal among the ten countries with the most patients identified. The cardiovascular risk of FH patients is determined by the high cholesterol values present since birth, but also by the pathogenicity of the identified variant. The early identification of these patients through genetic diagnosis allows the clinician to implement appropriate and more aggressive therapeutic measures in order to reduce the cardiovascular risk inherent to these patients.
Familial Hypercholesterolemia (FH) is a genetic disorder associated with a high cardiovascular risk. Patients with FH have very high plasma cholesterol values since birth. Until now three genes have been associated to FH: LDLR (85-90%), APOB (5-8%) and PCSK9 (1-2%). In 1999 the Portuguese FH (PFHS) Study was established at the National Institute of Health. This study aims to identify the genetic cause of dyslipidemia in patients with clinical diagnosis of FH. The Portuguese FH Study genetically identified 718 heterozygous patients with a pathogenic or probably pathogenic variant (according to ACMG guidelines) in one of the 3 genes associated to FH. In addition, 90 individuals have one of 35 variants of uncertain significance whose pathogenicity needs to be assessed through functional studies. Ten homozygotes (3 true homozygotes and 7 heterozygous compounds) were also identified, with pathogenic variants in the LDLR and PCSK9 genes. The PFHS was able to identify 3.8% of the Portuguese that are estimated to have FH, placing Portugal among the ten countries with the most patients identified. The cardiovascular risk of FH patients is determined by the high cholesterol values present since birth, but also by the pathogenicity of the identified variant. The early identification of these patients through genetic diagnosis allows the clinician to implement appropriate and more aggressive therapeutic measures in order to reduce the cardiovascular risk inherent to these patients.
Descrição
Palavras-chave
Hipercolesterolemia Familiar Doenças Cardio e Cérebro-vasculares Saúde Pública Portugal
Contexto Educativo
Citação
Boletim Epidemiológico Observações. 2017;6(Supl 9):15-18
Editora
Instituto Nacional de Saúde Doutor Ricardo Jorge, IP