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8 January 2026

Population Admixture and APOB Variant Landscape in Ecuadorian Mestizo Patients with Cardiac Diseases: Potential Implications for Familial Hypercholesterolemia Genetics

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1
Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Genéticay Genómica, Quito 170129, Ecuador
2
EXPRELA Research Group, CICA—Centro Interdisciplinar de Química e Bioloxía, Universida da Coruña (UDC), 15071 A Coruña, Spain
3
Instituto de Investigación Biomédica de A Coruña (INIBIC), As Xubias, 15006 A Coruña, Spain
4
Instituto de Investigación Biomédica de A Coruña (INIBIC)-CIBERCV, Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas, Universidad da Coruña (UDC), A Coruña 15006, Spain
This article belongs to the Special Issue Cardiovascular Disease in Patients with Familial Hypercholesterolemia

Abstract

Apolipoprotein B (APOB) is a key structural component of atherogenic lipoproteins and one of the principal genes implicated in familial hypercholesterolemia (FH). However, APOB genetic variation remains poorly characterized in Latin American and admixed populations. In this study, we performed a descriptive analysis of APOB variants in 60 Ecuadorian mestizo patients with inherited cardiac conditions using next-generation sequencing (NGS) and genetic ancestry inference. A total of 227 APOB variants were identified, the majority of which were classified as benign (n = 220) or likely benign (n = 3) according to ACMG criteria, while three variants were classified as variants of uncertain significance (VUS). The most frequently observed variants included rs1042034, rs679899, rs676210, and rs1367117. Comparative allele-frequency analyses using ALFA and PAGE Latin American reference datasets demonstrated that the APOB variant frequencies observed in the cohort were comparable to those reported in other Latin American populations, reflecting the admixed genetic background of Ecuadorian mestizos, predominantly of Native American and European ancestry. No pathogenic APOB variants were detected. Although lipid measurements were not available and genotype–phenotype associations could not be assessed, this study provides the first comprehensive overview of APOB variation in Ecuadorian mestizo individuals. These findings expand population-specific genomic data for an underrepresented group and underscore the importance of regional reference datasets for accurate variant interpretation in admixed populations.

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