Evidence mapPaperPMID 42318941Full record

ArticleJournal of diabetes research2026

Multiomics Integration Prioritizes ZFP36L1 as a Candidate Susceptibility Gene Associated With Inflammatory and Angiogenic Pathways in Diabetic Retinopathy.

Ruiqing Dong, Xiaoli Hui, Chenwen Luo, Shengnan Chen, Ning Gao, Mingqian He, Bingyin Shi, Wei Qiang

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Article in Journal of diabetes research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Ruiqing DongDepartment of Endocrinology and Metabolism, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China, xjtu.edu.cn.ORCID https://orcid.org/0000-0003-3583-5801
Xiaoli HuiDepartment of Endocrinology and Second Department of Geriatrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China, xjtu.edu.cn.ORCID https://orcid.org/0000-0003-4478-636X
Chenwen LuoDepartment of Clinical Medicine, Xi'an Medical University, Xi'an, China, xjtu.edu.cn.ORCID https://orcid.org/0009-0001-6661-9047
Shengnan ChenDepartment of Critical Care Nephrology and Blood Purification, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China, xjtu.edu.cn.ORCID https://orcid.org/0000-0003-0635-7724
Ning GaoDepartment of Ophthalmology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China, xjtu.edu.cn.ORCID https://orcid.org/0009-0006-2284-7351
Mingqian HeDepartment of Endocrinology and Metabolism, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China, xjtu.edu.cn.ORCID https://orcid.org/0009-0003-1239-5740
Bingyin ShiDepartment of Endocrinology and Metabolism, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China, xjtu.edu.cn.ORCID https://orcid.org/0000-0002-1505-8892
Wei QiangDepartment of Endocrinology and Metabolism, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China, xjtu.edu.cn.ORCID https://orcid.org/0000-0003-0701-2998

Funding

Key Research and Development Projects of Shaanxi Province 2021LL-JB-06Key Research and Development Projects of Shaanxi Province 2023-ZDLSF-40the Natural Science Foundation Program of Shaanxi 2024JC-YBQN-0828
6 · The paper itself

Abstract

backgroundDiabetic retinopathy (DR) is a prevalent microvascular complication of diabetes and a leading cause of blindness despite available therapies, underscoring the need for novel therapeutic targets.

methodsIntegrated multiomics analysis combining (1) exploratory single-cell RNA sequencing of rat retinal tissues (three DRs vs. two controls), (2) Mendelian randomization (MR) using whole-blood eQTL data and DR GWAS data (14,584 cases vs. 202,082 controls), and (3) supportive RT-qPCR validation in peripheral-blood clinical samples (30 DRs vs. 30 controls).

results(1) Genetic causality was as follows: MR analysis demonstrated ZFP36L1 as a novel DR risk gene (OR = 1.156, 95% CI = 1.054-1.269, p = 0.002), with significant upregulation in patient blood samples (p < 0.0001). (2) Inflammatory regulation was as follows: ZFP36L1 showed strong correlations with proinflammatory markers (TNF-α and IL-6) and immune cell infiltration (parainflammation and Tregs), while negatively correlating with B cells. (3) Pathway mechanisms were as follows: Functional enrichment analyses suggested potential links between ZFP36L1 and NF-κB-related inflammatory signaling as well as TGF-β-related angiogenic pathways. Despite its known VEGF mRNA destabilizing function, we observed a positive ZFP36L1-VEGF correlation (r = 0.180, p < 0.001), an unexpected finding under diabetic conditions.

conclusionsZFP36L1 is a candidate DR susceptibility gene whose genetically regulated expression in blood is associated with DR risk. Retinal single-cell and pathway analyses provide supportive, hypothesis-generating evidence that ZFP36L1 may be linked to inflammatory and angiogenic processes relevant to DR. Further retina-specific and functional studies are required to determine whether ZFP36L1 directly regulates retinal inflammation or angiogenesis in human DR.

Indexed as

Butyrate Response Factor 1Diabetic RetinopathyGenetic Predisposition to DiseaseInflammationAnimalsGenome-Wide Association StudyHumansMultiomicsRatsButyrate Response Factor 1ZFP36L1 protein, humandiabetic retinopathyinflammationMendelian randomizationNF-κB signalingsingle-cell RNA sequencingZFP36L1

Identifiers

PMID42318941
PMCPMC13280981

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.