Evidence map›Paper›PMID 40304587›Full record

ArticleJournal of diabetes investigation2025

A Mendelian randomization study on the causal association of circulating cytokines with diabetic nephropathy.

Yiming Xu, Tian Xiao, Junqing Yang, Jiali Wang, Bingting Wang, Chen Qiao

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Article in Journal of diabetes investigation, 2025. 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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5 · Who and what money

Authors and funding

6 authors.

Yiming XuSchool of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
Tian XiaoSchool of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.ORCID https://orcid.org/0009-0006-4196-8888
Junqing YangSchool of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
Jiali WangSchool of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
Bingting WangSchool of Pharmacy, China Pharmaceutical University, Nanjing, China.
Chen QiaoSchool of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.ORCID https://orcid.org/0000-0003-1311-056X

Funding

Basic Foundation for China Pharmaceutical Universities 2632021ZD17National Science Foundation for Young Scientists of China 81803565
6 · The paper itself

Abstract

backgroundCirculating cytokines were reported to be related to diabetic nephropathy (DN) in observational studies. However, the causal relationship between them remains unknown. This study aimed to investigate the causal relationship between DN and circulating cytokines with genetic data in the frame of Mendelian Randomization (MR).

methodsWe performed a two-sample MR analysis to investigate the causal relationship in individuals of European ancestry, utilizing publicly available genome-wide association study (GWAS) statistics. We selected eligible instrumental SNPs that were significantly related to the circulating cytokines. Multiple MR analysis approaches were employed, including inverse variance weighted (IVW), Weighted Median, MR-Egger, Weighted Mode, Simple Mode, and MR pleiotropy residual sum and outlier (MR-PRESSO) methods.

resultsWe found evidence supporting the causal role of genetically predicted circulating levels in the increased risk of DN. Specifically, we observed associations for interferon-gamma [OR = 1.352, 95% CI: 1.089-1.678, P = 0.006], stem cell factor [OR = 1.252, 95% CI: 1.028-1.525, P = 0.025], and stromal-cell-derived factor 1 alpha [OR = 1.326, 95% CI: 1.017-1.727, P = 0.037]. Additionally, MR analysis revealed a negative causal association between macrophage inflammatory protein 1b and DN [OR = 0.921, 95% CI: 0.858-0.988, P = 0.022]. The results obtained from MR-Egger, Weighted Median, Weighted Mode, and Simple Mode methods were consistent with the Inverse Variance Weighted (IVW) estimates. Sensitivity analyses showed no evidence of horizontal pleiotropy, suggesting that the causal estimates were not biased.

conclusionsOur findings offer promising leads for developing novel therapeutic targets for DN. By identifying the role of inflammatory cytokines in this debilitating condition through a genetic epidemiological approach, our study made contributions to a better understanding of the underlying disease mechanisms.

Indexed as

BiomarkersCytokinesDiabetic NephropathiesMendelian Randomization AnalysisGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotideBiomarkersCytokinesCirculating cytokinesDiabetic nephropathyMendelian randomization

Identifiers

PMID40304587
PMCPMC12209511

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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 OpenQuestion graph.