Chao_2026_J.Clin.Lipidol__

BACKGROUND: Chylomicronemia is a genetically heterogeneous condition with both genetic and environmental determinants. Genetic studies have largely focused on European populations, with limited data from East Asians, particularly Han Chinese. We characterized the genetic profiles of chylomicronemia patients of mainly Han Chinese ancestry in Taiwan. OBJECTIVE: To identify and classify disease-causing variants in chylomicronemia patients. METHODS: Capture-based targeted next-generation sequencing was performed for 108 chylomicronemia patients to assess hypertriglyceridemia-related genes, including those harboring large- and moderate-effect rare variants, and small-effect single-nucleotide variants. RESULTS: Twenty-seven patients (25%) carried large-effect, disease-causing rare variants, the majority in LPL (86%), with additional variants identified in APOA5, LMF1, and APOA1. The most prevalent variant, NM_000237.3(LPL):c.835C>G(p.L279V), was detected in all homozygous and compound heterozygous cases. Comparison with the Taiwan Biobank revealed significant differences in APOE allele and genotype distributions (P = .003492 and P = .009, respectively). Additionally, NM_001371904.1(APOA5): c.553G>T(p.G185C) was identified in 43.5% of patients, showing a high prevalence despite not being classified as a large-effect variant, and frequently found without additional large-effect rare variants. CONCLUSION: As one of the most comprehensive characterizations to date of chylomicronemia in an East Asian cohort, the predominance of large-effect LPL rare variants, together with the high prevalence of the APOA5 p.G185C variant and distinct APOE allele distributions, highlights population-specific genetic architecture.