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

IF 3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes Investigation Pub Date : 2025-04-30 DOI:10.1111/jdi.70051

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

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引用次数: 0

Abstract

Background

Circulating 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).

Methods

We 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.

Results

We 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.

Conclusions

Our 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.

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查看原文本刊更多论文

循环细胞因子与糖尿病肾病因果关系的孟德尔随机研究。

背景：观察性研究报道了循环细胞因子与糖尿病肾病（DN）有关。然而，它们之间的因果关系尚不清楚。本研究旨在探讨遗传数据在孟德尔随机化（MR）框架内DN和循环细胞因子之间的因果关系。方法：利用公开的全基因组关联研究（GWAS）统计数据，我们进行了两样本MR分析，以调查欧洲血统个体的因果关系。我们选择了与循环细胞因子显著相关的符合条件的仪器snp。采用了多种MR分析方法，包括逆方差加权（IVW）、加权中位数（weighted Median）、MR- egger、加权模式（weighted Mode）、简单模式（Simple Mode）和MR多效差残差和离群值（MR- presso）方法。结果：我们发现证据支持遗传预测的血液水平在DN风险增加中的因果作用。具体来说，我们观察到干扰素- γ [OR = 1.352, 95% CI: 1.089-1.678, P = 0.006]、干细胞因子[OR = 1.252, 95% CI: 1.028-1.525, P = 0.025]和基质细胞衍生因子1 α [OR = 1.326, 95% CI: 1.017-1.727, P = 0.037]的相关性。此外，MR分析显示巨噬细胞炎症蛋白1b与DN呈负相关[OR = 0.921, 95% CI: 0.858-0.988, P = 0.022]。MR-Egger、加权中位数、加权模态和简单模态方法得到的结果与逆方差加权（IVW）估计值一致。敏感性分析没有显示水平多效性的证据，表明因果估计没有偏倚。结论：我们的发现为开发新的DN治疗靶点提供了有希望的线索。通过遗传流行病学方法确定炎症细胞因子在这种衰弱状态中的作用，我们的研究有助于更好地理解潜在的疾病机制。

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来源期刊

Journal of Diabetes Investigation ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

9.40%

发文量

218

审稿时长

6-12 weeks

期刊介绍： Journal of Diabetes Investigation is your core diabetes journal from Asia; the official journal of the Asian Association for the Study of Diabetes (AASD). The journal publishes original research, country reports, commentaries, reviews, mini-reviews, case reports, letters, as well as editorials and news. Embracing clinical and experimental research in diabetes and related areas, the Journal of Diabetes Investigation includes aspects of prevention, treatment, as well as molecular aspects and pathophysiology. Translational research focused on the exchange of ideas between clinicians and researchers is also welcome. Journal of Diabetes Investigation is indexed by Science Citation Index Expanded (SCIE).