J Clin Lipidol. 2026 Jan 12:S1933-2874(26)00003-6. doi: 10.1016/j.jacl.2026.01.004. Online ahead of print.
ABSTRACT
BACKGROUND: The size, composition, and functionality of high-density lipoprotein cholesterol (HDL-C) are potential biomarkers for predicting atherosclerosis, representing a major advance in the prevention and treatment of cardiovascular diseases.
OBJECTIVE: This study aims to explore HDL-C concentrations and a derived HDL functionality score (HFS), and to investigate suggestive genetic associations in a representative Brazilian population.
METHODS: This is an observational cross-sectional study. Plasma lipid profiles were analyzed using an automated system. The Lipoprint System determined HDL particle sizes. HFS was calculated using a composite based on the large HDL particle concentration combined with relevant cardiovascular data from demographic and clinical parameters. After DNA extraction, genotyping, and quality control, information on 330,656 single-nucleotide polymorphisms (SNPs) was available for genome-wide association studies (GWAS) of HFS.
RESULTS: Among 345 participants, HDL functionality was impaired in 38%. Those with low functionality exhibited higher average waist circumference, systolic blood pressure, and glucose, as well as lower HDL-C concentrations, compared with those with high HDL functionality (P < .05). GWAS revealed suggestive associations for 5 SNPs and HFS, including rs11730709, rs78565063, and rs11786395 (P < 1 × 10-5), as well as rs12734338 and rs36019094 (P < 1 ×10-8). Additional regression analyses showed that SNPs rs12734338 and rs36019094 were positively associated with HFS, while rs11730709 showed an inverse association. Furthermore, rs12734338 increased the prevalence of low HFS by 41%, whereas rs11730709 reduced it by 34%.
CONCLUSION: These findings suggest potential genetic loci associated with the HFS, creating an opportunity for further investigations. Replication in larger and independent cohorts is warranted to confirm and extend these observations.
PMID:41622043 | DOI:10.1016/j.jacl.2026.01.004