A Novel Screening Approach for Familial Hypercholesterolemia: A Genetic Study on Patients Detected Using Preexisting...

Area of Science:

• Genetics
• Cardiovascular Medicine
• Biochemistry

Background:

• Familial hypercholesterolemia (FH) is a genetic disorder of lipid metabolism.
• It leads to high LDL-C and increased risk of atherosclerotic cardiovascular disease.
• Mutations in genes like LDLR are common causes of FH.

Purpose of the Study:

• To conduct a genetic study on individuals identified through a population-based FH screening program.
• To analyze genetic variants in key FH-related genes.
• To assess the correlation between genetic findings, clinical phenotype, and cardiovascular risk.

Main Methods:

• Genetic variants were analyzed in 84 individuals with a clinical FH diagnosis (DLCN ≥ 6).
• Genes studied included LDLR, APOB, APOE, PCSK9, STAP1, LDLRAP1, and LIPA.
• A genetic risk score was calculated for cardiovascular disease risk assessment.

Main Results:

• A clinical FH diagnosis was confirmed in 17.9% of screened patients, with mean LDL-C of 305.7 mg/dL.
• Genetic variants were found in 70.2% of diagnosed FH patients, with 50 mutations identified, primarily in LDLR.
• Null variants correlated with a more severe phenotype, and the risk score indicated a 42% higher cardiovascular disease risk.

Conclusions:

• A high prevalence of genetic alterations was observed in patients with severe FH.
• Phenotypic presentation often did not predict genetic findings.
• Genetic results are crucial for accurately assessing cardiovascular risk in FH patients.