Circulating inflammatory cytokines and gestational diabetes mellitus: Unraveling the role of macrophage migration inhibitory factor (MIF) through a bidirectional mendelian randomization study

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Cytokine Pub Date : 2024-08-09 DOI:10.1016/j.cyto.2024.156734

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Abstract

Background

Several studies have identified associations between some of circulating inflammatory cytokines and gestational diabetes mellitus (GDM). However, the causal role of these associations remains unclear and unsystematic. We aimed to provide evidence for the causal relationships between circulating inflammatory cytokines and gestational diabetes mellitus.

Methods

We performed bidirectional two-sample Mendelian randomization (2SMR) to investigate the causal connection between circulating inflammatory cytokines and gestational diabetes mellitus. Publicly accessible data for circulating inflammatory cytokines (8,293 individuals) and gestational diabetes mellitus (123,579 individuals) were obtained from genome-wide association study (GWAS).

Results

Only one causal association was identified between circulating inflammatory cytokines and GDM. The inverse variance weighting (IVW) method showed that macrophage migration inhibitory factor (MIF) increased the risk of GDM (OR 1.162, 95%CI 1.044,1.293). Moreover, two causal associations were detected between GDM and circulating inflammatory cytokines. GDM was negatively correlated with interferon gamma-induced protein 10 (IP10) (Beta −0.129, 95%CI −0.236,-0.231) and interleukin-18 (IL18) (Beta −0.133, 95%CI −0.241,-0.026).

Conclusion

Mendelian randomization study revealed MIF as a risk factor for gestational diabetes mellitus. This finding offers a new and valuable insight into the pathophysiological mechanisms underlying GDM.

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循环炎症细胞因子与妊娠糖尿病：通过双向泯灭随机研究揭示巨噬细胞迁移抑制因子 (MIF) 的作用。

背景：多项研究发现，一些循环炎性细胞因子与妊娠糖尿病（GDM）之间存在关联。然而，这些关联的因果关系仍不明确，也不系统。我们旨在为循环炎性细胞因子与妊娠糖尿病之间的因果关系提供证据：方法：我们采用双向双样本孟德尔随机法（2SMR）研究了循环炎性细胞因子与妊娠糖尿病之间的因果关系。从全基因组关联研究（GWAS）中获得了循环炎性细胞因子（8,293 人）和妊娠糖尿病（123,579 人）的公开数据：结果：在循环炎性细胞因子与妊娠糖尿病之间只发现了一种因果关系。逆方差加权法（IVW）显示，巨噬细胞迁移抑制因子（MIF）会增加罹患 GDM 的风险（OR 1.162，95%CI 1.044,1.293）。此外，还发现 GDM 与循环炎症细胞因子之间存在两种因果关系。GDM与干扰素γ诱导蛋白10（IP10）（Beta -0.129，95%CI -0.236,-0.231）和白细胞介素18（IL18）（Beta -0.133，95%CI -0.241,-0.026）呈负相关：结论：孟德尔随机研究揭示了 MIF 是妊娠糖尿病的一个风险因素。结论：孟德尔随机化研究发现 MIF 是妊娠糖尿病的危险因素，这一发现为了解妊娠糖尿病的病理生理机制提供了新的有价值的视角。

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.