Genomic exploration of atherogenic lipoproteins in a Caribbean population: findings from the Genesis-Athero Study

Abstract

Background: Inherited dyslipidemias, including familial hypercholesterolemia (FH), contribute to premature atherosclerotic cardiovascular disease (ASCVD). The genetic landscape of these disorders remains unexplored in the Caribbean. Methods: A cross-sectional study was conducted on 17 adults who underwent genetic testing from a registry of 465 patients with suspected inherited dyslipidemia (2022-2025). Targeted sequencing analyzed lipid-related genes (LDLR, APOB, PCSK9, APOA5, APOE, GCKR, LRP6, GPD1, LIPC, GALNT2). Data on zygosity, inheritance, ClinVar classification, comorbidities, and lipid phenotypes were recorded. Results: Heterozygous variants with autosomal dominant inheritance predominated (100%). Pathogenic LDLR variants (c.590G>A, c.331C>T) confirmed classical FH in 11.8% of cases. The most frequent variants were APOA5 and APOE (35.3% each), associated with hypertension (HTN, 64.7%), diabetes/prediabetes (DM/Pre-DM, 35.3%), and coronary artery disease (CAD, 29.4%). A TRL-risk heatmap identified them as major contributors to residual atherogenic risk.