Prediagnostic Plasma Metabolomic Profiles Using NMR for Exfoliation Glaucoma Among US Health Professionals

Background: Exfoliation glaucoma (XFG) represents a form of deleterious ocular aging of unclear etiology. We evaluated prediagnostic nuclear magnetic resonance (NMR)-based metabolites in relation to XFG risk, expanding on our prior findings of XFG-related metabotypes using liquid chromatography-mass...

Full description

Saved in:
Bibliographic Details
Main Authors: Akiko Hanyuda, Oana A. Zeleznik, Yoshihiko Raita, Danielle E. Haslam, Qi Sun, Kazuno Negishi, Louis R. Pasquale, Jessica Lasky-Su, Janey L. Wiggs, Jae H. Kang
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Metabolites
Subjects:
Online Access:https://www.mdpi.com/2218-1989/15/7/469
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849246517731262464
author Akiko Hanyuda
Oana A. Zeleznik
Yoshihiko Raita
Danielle E. Haslam
Qi Sun
Kazuno Negishi
Louis R. Pasquale
Jessica Lasky-Su
Janey L. Wiggs
Jae H. Kang
author_facet Akiko Hanyuda
Oana A. Zeleznik
Yoshihiko Raita
Danielle E. Haslam
Qi Sun
Kazuno Negishi
Louis R. Pasquale
Jessica Lasky-Su
Janey L. Wiggs
Jae H. Kang
author_sort Akiko Hanyuda
collection DOAJ
description Background: Exfoliation glaucoma (XFG) represents a form of deleterious ocular aging of unclear etiology. We evaluated prediagnostic nuclear magnetic resonance (NMR)-based metabolites in relation to XFG risk, expanding on our prior findings of XFG-related metabotypes using liquid chromatography-mass spectrometry (LC-MS). Methods: We identified 217 XFG cases and 217 matched controls nested within three prospective health professional cohorts with plasma collected a mean 11.8 years before case identification. Plasma metabolites were analyzed using the targeted NMR Nightingale platform. Conditional logistic models and Metabolite Set Enrichment Analysis were performed. Multiple comparison issues were addressed using the number of effective tests (NEF) and false discovery rate (FDR). Results: Among 235 profiled metabolites, higher glucose was significantly associated with a lower risk of XFG (odds ratio (95%CI) = 0.42 (0.26, 0.7); NEF = 0.03). Among metabolite classes, lipoprotein subclasses and branched-chain amino acids were inversely associated, while relative lipoprotein lipid concentrations were adversely associated (FDR < 0.05). Conclusion: NMR profiling revealed that glucose, branched-chain amino acids, lipoprotein subclasses, and relative lipoprotein lipid concentrations may play important roles in XFG etiology.
format Article
id doaj-art-d3875a41065f41f0a3d8d8d8ce46fb59
institution Kabale University
issn 2218-1989
language English
publishDate 2025-07-01
publisher MDPI AG
record_format Article
series Metabolites
spelling doaj-art-d3875a41065f41f0a3d8d8d8ce46fb592025-08-20T03:58:27ZengMDPI AGMetabolites2218-19892025-07-0115746910.3390/metabo15070469Prediagnostic Plasma Metabolomic Profiles Using NMR for Exfoliation Glaucoma Among US Health ProfessionalsAkiko Hanyuda0Oana A. Zeleznik1Yoshihiko Raita2Danielle E. Haslam3Qi Sun4Kazuno Negishi5Louis R. Pasquale6Jessica Lasky-Su7Janey L. Wiggs8Jae H. Kang9Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, JapanChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USADepartment of Nephrology, Okinawa Prefectural Chubu Hospital, Naha 904-2293, JapanChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USAChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USADepartment of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USAChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USADepartment of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USAChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USABackground: Exfoliation glaucoma (XFG) represents a form of deleterious ocular aging of unclear etiology. We evaluated prediagnostic nuclear magnetic resonance (NMR)-based metabolites in relation to XFG risk, expanding on our prior findings of XFG-related metabotypes using liquid chromatography-mass spectrometry (LC-MS). Methods: We identified 217 XFG cases and 217 matched controls nested within three prospective health professional cohorts with plasma collected a mean 11.8 years before case identification. Plasma metabolites were analyzed using the targeted NMR Nightingale platform. Conditional logistic models and Metabolite Set Enrichment Analysis were performed. Multiple comparison issues were addressed using the number of effective tests (NEF) and false discovery rate (FDR). Results: Among 235 profiled metabolites, higher glucose was significantly associated with a lower risk of XFG (odds ratio (95%CI) = 0.42 (0.26, 0.7); NEF = 0.03). Among metabolite classes, lipoprotein subclasses and branched-chain amino acids were inversely associated, while relative lipoprotein lipid concentrations were adversely associated (FDR < 0.05). Conclusion: NMR profiling revealed that glucose, branched-chain amino acids, lipoprotein subclasses, and relative lipoprotein lipid concentrations may play important roles in XFG etiology.https://www.mdpi.com/2218-1989/15/7/469exfoliation glaucomametabolomicsnuclear magnetic resonance spectrometryomics
spellingShingle Akiko Hanyuda
Oana A. Zeleznik
Yoshihiko Raita
Danielle E. Haslam
Qi Sun
Kazuno Negishi
Louis R. Pasquale
Jessica Lasky-Su
Janey L. Wiggs
Jae H. Kang
Prediagnostic Plasma Metabolomic Profiles Using NMR for Exfoliation Glaucoma Among US Health Professionals
Metabolites
exfoliation glaucoma
metabolomics
nuclear magnetic resonance spectrometry
omics
title Prediagnostic Plasma Metabolomic Profiles Using NMR for Exfoliation Glaucoma Among US Health Professionals
title_full Prediagnostic Plasma Metabolomic Profiles Using NMR for Exfoliation Glaucoma Among US Health Professionals
title_fullStr Prediagnostic Plasma Metabolomic Profiles Using NMR for Exfoliation Glaucoma Among US Health Professionals
title_full_unstemmed Prediagnostic Plasma Metabolomic Profiles Using NMR for Exfoliation Glaucoma Among US Health Professionals
title_short Prediagnostic Plasma Metabolomic Profiles Using NMR for Exfoliation Glaucoma Among US Health Professionals
title_sort prediagnostic plasma metabolomic profiles using nmr for exfoliation glaucoma among us health professionals
topic exfoliation glaucoma
metabolomics
nuclear magnetic resonance spectrometry
omics
url https://www.mdpi.com/2218-1989/15/7/469
work_keys_str_mv AT akikohanyuda prediagnosticplasmametabolomicprofilesusingnmrforexfoliationglaucomaamongushealthprofessionals
AT oanaazeleznik prediagnosticplasmametabolomicprofilesusingnmrforexfoliationglaucomaamongushealthprofessionals
AT yoshihikoraita prediagnosticplasmametabolomicprofilesusingnmrforexfoliationglaucomaamongushealthprofessionals
AT danielleehaslam prediagnosticplasmametabolomicprofilesusingnmrforexfoliationglaucomaamongushealthprofessionals
AT qisun prediagnosticplasmametabolomicprofilesusingnmrforexfoliationglaucomaamongushealthprofessionals
AT kazunonegishi prediagnosticplasmametabolomicprofilesusingnmrforexfoliationglaucomaamongushealthprofessionals
AT louisrpasquale prediagnosticplasmametabolomicprofilesusingnmrforexfoliationglaucomaamongushealthprofessionals
AT jessicalaskysu prediagnosticplasmametabolomicprofilesusingnmrforexfoliationglaucomaamongushealthprofessionals
AT janeylwiggs prediagnosticplasmametabolomicprofilesusingnmrforexfoliationglaucomaamongushealthprofessionals
AT jaehkang prediagnosticplasmametabolomicprofilesusingnmrforexfoliationglaucomaamongushealthprofessionals