Korean Circ J.
2024 Nov;54(11):726-738. 10.4070/kcj.2024.0107.
Enhancing Familial Hypercholesterolemia Detection in South Korea: A Targeted Screening Approach Integrating National Program and Genetic Cascade Screening
- Affiliations
-
- 1Chonnam National University Hospital Cardio-Cerebrovascular Center, Gwangju, Korea
- 2Department of Preventive Medicine, Chonnam National University Medical School, Hwasun, Korea
- 3Department of Cardiology, Chonnam National University Medical School, Hwasun, Korea
- KMID: 2560660
- DOI: http://doi.org/10.4070/kcj.2024.0107
Abstract
- Background and Objectives
Familial hypercholesterolemia (FH) increases the risk of premature cardiovascular disease through disrupted low-density lipoprotein cholesterol (LDL-C) metabolism. Although FH is a severe condition, it remains widely underdiagnosed, which can be attributed to barriers in genetic testing and a lack of awareness. This study aims to propose and evaluate a targeted screening program for FH in South Korea by integrating the General Health Screening Program (GHSP) with cascade genetic screening.
Methods
The study included individuals with LDL-C levels ≥190 mg/dL identified during the 2021 GHSP (primary participants). Data on demographics, lifestyle, medical history, and family history were collected through questionnaires. Targeted next-generation sequencing was used to identify pathogenic mutations in the PCSK9, APOB, LDLRAP1, and LDLR genes associated with FH. Pathogenic mutations found in primary participants were confirmed in their relatives (secondary participants) using Sanger sequencing. Participant characteristics were analyzed based on the presence of pathogenic mutations.
Results
Among 83 individuals with severe hypercholesterolemia identified through the GHSP, 7 primary participants (8.4%) carried pathogenic mutations in the LDLR and PCSK9 genes. In secondary participants, pathogenic mutations were identified in 61.1% of the relatives of 4 patients with pathogenic mutations. The prevalence of pathogenic mutations was significantly higher in primary participants compared to secondary participants.
Conclusions
Integrating community resources with FH screening can enhance the early detection and treatment of FH. By utilizing GHSP data and adding genetic screening, the proposed model provides a strategy to reduce the cardiovascular risks associated with FH, supporting its wider adoption at the national level.
