Genetic and polygenic contributions to familial hypercholesterolemia in Thailand: Implications for diagnosis and lipid management
2
Issued Date
2025-01-01
Resource Type
ISSN
19332874
eISSN
18764789
Scopus ID
2-s2.0-105011646641
Journal Title
Journal of Clinical Lipidology
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SCOPUS
Bibliographic Citation
Journal of Clinical Lipidology (2025)
Suggested Citation
Pasookhush P., Surawit A., Suta S., Pumeiam S., Mongkolsucharitkul P., Pinsawas B., Ophakas S., Mayurasakorn K. Genetic and polygenic contributions to familial hypercholesterolemia in Thailand: Implications for diagnosis and lipid management. Journal of Clinical Lipidology (2025). doi:10.1016/j.jacl.2025.06.020 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/111466
Title
Genetic and polygenic contributions to familial hypercholesterolemia in Thailand: Implications for diagnosis and lipid management
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Abstract
BACKGROUND: Familial hypercholesterolemia (FH) is a major risk factor for cardiovascular diseases; however, the issue of underdiagnosis remains a global challenge. This study investigates the prevalence of FH-associated variants in Thailand and examines the clinical and lipid profile characteristics of variant carriers to improve diagnostic strategies. METHODS: We analyzed the genetic data of 4879 participants across 2 cohorts, identifying variants in LDLR, APOB, and PCSK9. A 12-single-nucleotide polymorphism (12-SNP) polygenic risk score (PRS) for low-density lipoprotein cholesterol (LDL-C) was calculated. Longitudinal lipid profiles, including LDL-C, total cholesterol (TC), triglyceride, and high-density lipoprotein cholesterol (HDL-C) were assessed to evaluate the sustained impact of FH-associated variants. RESULTS: FH-associated variants were identified in 0.59% of participants, with 68.96% carrying variants in LDLR and 31.04% in APOB. FH-associated variant carriers had significantly higher LDL-C (125.5 mg/dL vs 107.8 mg/dL, P =0.015) and TC levels (208.5 mg/dL vs 190.0 mg/dL, P = .004) than noncarriers, though overlap in lipid profiles was observed. PRS analysis revealed that FH-associated variants contributed more significantly to LDL-C levels than polygenic factors. Long-term follow-up showed persistent elevation of LDL-C and TC in FH-associated variant carriers. CONCLUSION: This study provides the first prevalence analysis of FH in Thailand, highlighting the limitations of lipid-based diagnostic criteria. Incorporating genetic screening and developing tailored diagnostic criteria are critical for addressing FH underdiagnosis and improving lipid management in Thailand.