Association between plasma free fatty acid levels and primary angle-closure glaucoma based on a mass spectrometry metabolomics analysis

Abstract

Purpose: To determine the association between plasma free fatty acid (FFA) levels and primary angle-closure glaucoma (PACG).

Methods: Free fatty acid (FFA) levels in patients with PACG (n = 181) and people without glaucoma (n = 340) were compared. Twenty-two FFAs and six lipid classes were measured using metabolomics analysis. Odds ratio (OR) of these metabolites and their 95% confidence intervals (95%CI) for PACG were obtained by logistic regression. Stepwise forward selection was performed to identify FFAs that influenced PACG risk. Areas under the curve (AUC) were applied to assess the predictive performance. Spearman's rank correlation was used to assess the relationship between ocular parameters and FFAs.

Results: Most FFAs in the PACG group were lower than those in the non-glaucoma group. Docosahexaenoic acid (DHA; OR for fourth quartile (Q4) vs. first quartile (Q1): 0.32 (0.16-0.66); per standard deviation (SD) increase: 0.64 (0.49-0.83); p for trend: 0.0007) and total saturated fatty acids (SFAs; OR for Q4 versus Q1: 0.27 (0.13-0.56); per SD increase: 0.65 (0.50-0.87); p for trend: 0.0004) were associated with decreased PACG risk. The AUC of the model that included DHA, total SFAs, demographic and ophthalmic factors increased from 0.8230 (0.7811-0.8649) to 0.8512 (0.8133-0.8891) (increased AUC: 0.0282 (0.0112-0.0453); p for increased AUC: 0.0012). Additionally, the cup-disc ratio had a weak negative correlation with DHA and total SFAs (DHA: r = -0.12085, p = 0.0065; total SFAs: r = -0.13318, p = 0.0024).

Conclusions: Decrease in FFA levels may be related to lipid peroxidation. Docosahexaenoic acid (DHA) and total SFAs may be screening indices for PACG patients.

Keywords: DHA; PACG; free fatty acid; lipid peroxidation; metabolomics analysis.