UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

A Metabolome-Wide Study of Dry Eye Disease Reveals Serum Androgens as Biomarkers

Vehof, J; Hysi, PG; Hammond, CJ; (2017) A Metabolome-Wide Study of Dry Eye Disease Reveals Serum Androgens as Biomarkers. Ophthalmology , 124 (4) pp. 505-511. 10.1016/j.ophtha.2016.12.011. Green open access

[thumbnail of Published article]
Preview
Text (Published article)
1-s2.0-S0161642016310570-main.pdf - Published Version

Download (695kB) | Preview
[thumbnail of Supplementary tables]
Preview
Text (Supplementary tables)
Vehof_Metabolome-Wide_Study_Suppl.pdf

Download (1MB) | Preview

Abstract

PURPOSE: To test the association between serum metabolites and dry eye disease (DED) using a hypothesis-free metabolomics approach. DESIGN: Cross-sectional association study. PARTICIPANTS: A total of 2819 subjects from the population-representative TwinsUK cohort in the United Kingdom, with a mean age of 57 years (range, 17-82 years). METHODS: We tested associations between 222 known serum metabolites and DED. All subjects underwent nontargeted metabolomic analysis of plasma samples using gas and liquid chromatography in combination with mass spectrometry (Metabolon Inc., Durham, NC). Dry eye disease was defined from the validated Short Questionnaire for Dry Eye Syndrome (SQDES) as a previous diagnosis of DED by a clinician or "often" or "constant" symptoms of dryness and irritation. Analyses were performed with linear mixed effect models that included age, BMI, and sex as covariates, corrected for multiple testing. MAIN OUTCOME MEASURES: Primary outcome was DED as defined by the SQDES, and secondary outcomes were symptom score of DED and a clinical diagnosis of DED. RESULTS: Prevalence of DED as defined by the SQDES was 15.5% (n = 436). A strong and metabolome-wide significant association with DED was found with decreased levels of the metabolites androsterone sulfate (P = 0.00030) and epiandrosterone sulfate (P = 0.00036). Three other metabolites involved in androgen metabolism, 4-androsten-3beta,17beta-diol disulfate 1 and 2, and dehydroepiandrosterone sulfate, were the next most strongly associated of the 222 metabolites, but did not reach metabolome-wide significance. Dryness and irritation symptoms, as opposed to a clinical diagnosis, were particularly strongly associated with decreased androgen steroid metabolites, with all reaching metabolome-wide significance (androsterone sulfate, P = 0.000000029; epiandrosterone sulfate, P = 0.0000040; 4-androsten-3beta,17beta-diol disulfate 1, P = 0.000016; 4-androsten-3beta,17beta-diol disulfate 2, P = 0.000064; and dehydroepiandrosterone sulfate, P = 0.00011). Of these 5 androgens, epiandrosterone sulfate (P = 0.0076) was most associated with 2-year incidence of clinician-diagnosed DED. In addition, we found decreased glycerophosphocholines to be associated with DED, although not at metabolome-wide significance. CONCLUSIONS: This hypothesis-free metabolomic approach found decreased serum androgens to be highly associated with DED and adds important evidence to the growing body of research that links androgens to ocular surface disease and DED.

Type: Article
Title: A Metabolome-Wide Study of Dry Eye Disease Reveals Serum Androgens as Biomarkers
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ophtha.2016.12.011
Publisher version: https://doi.org/10.1016/j.ophtha.2016.12.011
Language: English
Additional information: Copyright © 2017 by the American Academy of Ophthalmology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Population, Policy and Practice Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10042147
Downloads since deposit
141Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item