Unraveling the mechanisms underlying diabetic cataracts: insights from Mendelian randomization analysis

Background Diabetic cataract (DC) is a major cause of blindness, with its pathogenesis involving oxidative stress and ferroptosis, according to recent studies.Methods We performed a Mendelian Randomization (MR) study using GWAS data to select SNPs and assess the causal link between diabetes and cata...

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Main Authors: Wenlan Liu, Yiming Pan
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Redox Report
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Online Access:https://www.tandfonline.com/doi/10.1080/13510002.2024.2420563
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author Wenlan Liu
Yiming Pan
author_facet Wenlan Liu
Yiming Pan
author_sort Wenlan Liu
collection DOAJ
description Background Diabetic cataract (DC) is a major cause of blindness, with its pathogenesis involving oxidative stress and ferroptosis, according to recent studies.Methods We performed a Mendelian Randomization (MR) study using GWAS data to select SNPs and assess the causal link between diabetes and cataracts. DC datasets were analyzed for differential gene expression, WGCNA, and protein-protein interactions to identify key oxidative stress and ferroptosis genes. An SVM-RFE algorithm developed a diagnostic model, and ImmuCellAI analyzed immune infiltration patterns.Results MR analysis confirmed diabetes as a cataract risk factor and identified core genes related to oxidative stress and ferroptosis in DC. Four key genes (Hspa5/Nfe2l2/Atf3/Stat3) linked to both processes were discovered. Immune infiltration analysis revealed an imbalance associated with these genes.Conclusions A functional interaction between oxidative stress and ferroptosis genes in DC is suggested, with a 4-gene model, indicating their potential as a ‘bridge' in DC pathogenesis.
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spelling doaj-art-46f40c655eec4b64978dcbcf290e069a2024-12-07T06:20:30ZengTaylor & Francis GroupRedox Report1351-00021743-29282024-12-0129110.1080/13510002.2024.2420563Unraveling the mechanisms underlying diabetic cataracts: insights from Mendelian randomization analysisWenlan Liu0Yiming Pan1College of Medical Technology, Xi'an Medical University, Xi'an, People’s Republic of ChinaCollege of Medical Technology, Xi'an Medical University, Xi'an, People’s Republic of ChinaBackground Diabetic cataract (DC) is a major cause of blindness, with its pathogenesis involving oxidative stress and ferroptosis, according to recent studies.Methods We performed a Mendelian Randomization (MR) study using GWAS data to select SNPs and assess the causal link between diabetes and cataracts. DC datasets were analyzed for differential gene expression, WGCNA, and protein-protein interactions to identify key oxidative stress and ferroptosis genes. An SVM-RFE algorithm developed a diagnostic model, and ImmuCellAI analyzed immune infiltration patterns.Results MR analysis confirmed diabetes as a cataract risk factor and identified core genes related to oxidative stress and ferroptosis in DC. Four key genes (Hspa5/Nfe2l2/Atf3/Stat3) linked to both processes were discovered. Immune infiltration analysis revealed an imbalance associated with these genes.Conclusions A functional interaction between oxidative stress and ferroptosis genes in DC is suggested, with a 4-gene model, indicating their potential as a ‘bridge' in DC pathogenesis.https://www.tandfonline.com/doi/10.1080/13510002.2024.2420563Diabetic cataractoxidative stressferroptosisimmune infiltrationMendelian randomizationHspa5
spellingShingle Wenlan Liu
Yiming Pan
Unraveling the mechanisms underlying diabetic cataracts: insights from Mendelian randomization analysis
Redox Report
Diabetic cataract
oxidative stress
ferroptosis
immune infiltration
Mendelian randomization
Hspa5
title Unraveling the mechanisms underlying diabetic cataracts: insights from Mendelian randomization analysis
title_full Unraveling the mechanisms underlying diabetic cataracts: insights from Mendelian randomization analysis
title_fullStr Unraveling the mechanisms underlying diabetic cataracts: insights from Mendelian randomization analysis
title_full_unstemmed Unraveling the mechanisms underlying diabetic cataracts: insights from Mendelian randomization analysis
title_short Unraveling the mechanisms underlying diabetic cataracts: insights from Mendelian randomization analysis
title_sort unraveling the mechanisms underlying diabetic cataracts insights from mendelian randomization analysis
topic Diabetic cataract
oxidative stress
ferroptosis
immune infiltration
Mendelian randomization
Hspa5
url https://www.tandfonline.com/doi/10.1080/13510002.2024.2420563
work_keys_str_mv AT wenlanliu unravelingthemechanismsunderlyingdiabeticcataractsinsightsfrommendelianrandomizationanalysis
AT yimingpan unravelingthemechanismsunderlyingdiabeticcataractsinsightsfrommendelianrandomizationanalysis