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Mutational analysis and genotype-phenotype relation in familial hypercholesterolemia: The SAFEHEART registry

Mafalda Bourbon1, Ana Catarina Alves1, Rodrigo Alonso2

  • 1Unidade de I&D, Grupo de Investigação Cardiovascular, Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal; BioISI - Biosystems & Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal.

Atherosclerosis
|May 6, 2017
PubMed

Insights

This study analyzed genetic variants in Familial Hypercholesterolemia (FH) patients from the SAFEHEART registry. Most patients had pathogenic variants, with null variants linked to a more severe cholesterol metabolism phenotype.

Area of Science:

  • Genetics
  • Metabolic Diseases
  • Cardiovascular Health

Background:

  • Familial Hypercholesterolemia (FH) is an inherited disorder of cholesterol metabolism.
  • FH significantly increases the risk of premature atherosclerotic cardiovascular disease (ASCVD).
  • Early diagnosis and treatment are crucial for improving patient prognosis and reducing cardiovascular mortality.

Purpose of the Study:

  • To conduct a comprehensive mutational analysis of individuals within the SAFEHEART registry.
  • To identify genetic variants associated with Familial Hypercholesterolemia.
  • To correlate molecular findings with phenotypic expression in FH patients.

Main Methods:

  • Recruitment of 2938 individuals with a genetic diagnosis of FH from 775 families.
  • Detailed mutational analysis of the SAFEHEART cohort.
  • Statistical analysis using SPSS v23.

Main Results:

  • Detection of 194 genetic variants, including 24 novel ones.
  • Approximately 88% of patients harbored pathogenic or likely pathogenic variants.
  • Patients with null variants exhibited a more severe phenotype, with higher levels of atherogenic particles.

Conclusions:

  • The study characterizes the molecular landscape of FH within the SAFEHEART registry.
  • A high proportion of pathogenic variants confirms the registry's data reliability for FH research.
  • Findings highlight the link between specific genetic variants and FH phenotype severity, impacting prognosis and treatment strategies.
Abstract

Keywords:
Atherogenic lipoprotein particlesDefective variantsFamilial hypercholesterolemiaMutational analysisNull variants

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