Purchase this article with an account.
Adriana I Iglesias, Henriet Springelkamp, Sven van der Lee, Ayse Demirkan, Aswin Verhoeven, Gerd Schmitz, Ko Willems van Dijk, Thomas Hankemeier, Caroline C W Klaver, Cornelia M van Duijn; Identification of plasma metabolites associated with intraocular pressure in a Dutch family-based study. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3655.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Recent proteomic studies have found various lipoproteins that regulate lipid metabolism in the circulation and central nervous system. Moreover, components of the metabolic syndrome, particularly dyslipidemia and obesity, have shown to be associated with intraocular pressure (IOP). This raises the question whether specific apolipoproteins, cholesterol sub-fractions and phospholipids influence and are associated with IOP and glaucoma. We have addressed this question in a family-based cohort, the Erasmus Rucphen Family (ERF) Study
Subjects from ERF were extensively phenotyped using five metabolite platforms; one set by the AbsoluteIDQTM p150 Kit (Biocrates Life Sciences AG) (N-subjects=992), two sets by nuclear magnetic resonance spectroscopy (N=2416 and N=2609) and two sets by mass spectrometry (N=2592 and N=878). IOP measurements were available for N=2277 subjects, the mean IOP of both eyes was used in the analyses. Partial correlation was performed to evaluate correlation between 562 metabolite measures with IOP adjusting for age, gender, and lipid lowering therapy. The number of independent tests yielded a threshold of p<2.4E-4(0.05/200)
In total we found 96 significant correlations with IOP (p<2.4E-04). Correlations were found for various lipid fractions including LDL bound triglycerides (r=0.31, p=1.31E-56), lipid-bound and plasma ApoB (r=0.23,p=1.10E-30), lipid-bound and plasma ApoA1(r=0.18, p=1.95E-19), and lipid-bound and plasma ApoA2 (r=0.17, p=1.46E-18). Inverse correlations were found for HDL bound free-cholesterol (r=-0.22, p=2.47E-28), phospholipids (r=-0.12, p=1.58E-09) and different phosphatidylcholine species (r=-0.22, p=1.61E-11). When the classical circulating lipids (triglycerides, HDL and LDL-cholesterol) were analysed, direction of the correlation was consistent but p-value did not exceed the threshold of significance
Our dense metabolome search indicates that various metabolites, particularly species that are in the triglycerides, LDL and ApoB axes, positive correlate with IOP; while HDL free-cholesterol and phospholipids decrease IOP. Similar to previous proteomic studies we found ApoA1 and ApoA2 to be strongly correlated with IOP. Our findings suggest that blood-based lipid sub-fractions may represent etiological pathways relevant to IOP and should be studied as potential biomarkers to glaucoma
This PDF is available to Subscribers Only