HDL3 cholesterol tied to primary open-angle glaucoma

A causal and specific association exists between high-density lipoprotein (HDL) 3 cholesterol and primary open-angle glaucoma (POAG), suggests a cross-sectional study, noting that dysregulation of cholesterol transport may contribute to the pathogenesis of POAG.

A total of 8,503 individuals were recruited for the baseline visit of the population-based Singapore Epidemiology of Eye Disease study and underwent detailed standardized ocular and systemic examinations. A nuclear magnetic resonance metabolomics platform was used to quantify 130 blood lipid-related metabolites.

The investigators conducted the analyses in two stages: First, they determined whether and which lipid-related metabolites were directly associated with POAG using regression analyses, followed by Bayesian network modeling; second, they verified whether a causal relationship exists between the identified lipid-related metabolites and POAG using two-sample Mendelian randomization analysis (MR).

Finally, genome-wide association studies (GWAS) were carried out on HDL3 cholesterol (after inverse normal transformation), and top variants associated with HDL3 cholesterol were used as instrumental variables (IVs) in the MR analysis.

Of the participants, only 175 (2.1 percent) presented with POAG. In a logistic regression model, total HDL3 cholesterol negatively while phospholipids in very large HDL positively correlated with POAG.

Analyses using a Bayesian network analysis revealed that only total HDL3 cholesterol directly correlated with POAG (odds ratio [OR], 0.72 per 1 standard deviation increase in HDL3 cholesterol, 95 percent confidence interval [CI], 0.61‒0.84), independently of age, gender, intraocular pressure (IOP), body mass index (BMI), education level, systolic blood pressure, axial length, and statin medication.

Higher levels of HDL3 cholesterol were associated with a lower likelihood of POAG (OR, 0.91, 95 percent CI, 0.84‒0.99; p=0.021) when using five IVs identified from the GWAS and with the inverse variance weighted MR method. Consistent OR estimates were obtained when using other MR methods, such as weighted median, mode-based estimator, and contamination mixture methods.

Furthermore, none of the routine lipids (blood total, HDL, or low-density lipoprotein cholesterol) correlated with POAG.