Exploring the genetic association between inflammatory cytokines and primary ovarian insufficiency: A Mendelian randomization study

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-04-03 DOI:10.1016/j.cyto.2025.156937

Jie Wu , Yancheng Fu , Zhengqi Qiu

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引用次数: 0

Abstract

Purpose: This study aims to investigate the genetic underpinnings of Primary Ovarian Insufficiency (POI) by examining the association between 91 inflammatory cytokines identified through genome-wide association studies (GWAS) and POI, using Mendelian randomization (MR) to explore potential causal relationships.

Methods: We utilized Mendelian Randomization (MR) to investigate the causative links between inflammatory cytokines and POI, selecting genetic variants associated with cytokine levels as instrumental variables.

Results: Utilizing the Inverse Variance Weighted (IVW) method, our Mendelian Randomization (MR) study elucidated the influence of inflammatory cytokines on POI. We discovered that certain cytokines exhibit a protective association: CC motif chemokine 19 (CCL19) [OR 0.58; 95 % CI: 0.36–0.93; p = 0.024], Interleukin-10 (IL-10) [OR 0.41; 95 % CI: 0.23–0.72; p = 0.002], Interleukin-17 A (IL-17 A) [OR 0.44; 95 % CI: 0.20–0.96; p = 0.040], and Monocyte chemotactic protein 3 (MCP-3) [OR 0.51; 95 % CI: 0.29–0.89; p = 0.018]. Conversely, an elevated level of interleukin-33 in blood plasma was identified as a risk factor for POI [OR 2.83; 95 % CI: 1.23–6.50; p = 0.015].

Conclusion: Our findings indicate a significant correlation between specific inflammatory cytokines and the risk of developing POI. The negative association of cytokines such as CCL19, IL-10, IL-17 A, and MCP-3 suggests a protective effect against POI, whereas the positive association of IL-33 levels implies a potential adverse impact. These insights could guide future research towards targeted immunomodulatory therapies for the management and prevention of POI.

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探索炎症细胞因子与原发性卵巢功能不全之间的遗传关联：一项孟德尔随机研究

目的：本研究旨在通过研究全基因组关联研究（GWAS）鉴定的91种炎症细胞因子与原发性卵巢功能不全（POI）之间的关系，利用孟德尔随机化（MR）探索潜在的因果关系，探讨原发性卵巢功能不全（POI）的遗传基础。方法：我们使用孟德尔随机化（MR）来研究炎症细胞因子与POI之间的因果关系，选择与细胞因子水平相关的遗传变异作为工具变量。结果：利用逆方差加权（IVW）方法，我们的孟德尔随机化（MR）研究阐明了炎症因子对POI的影响。我们发现某些细胞因子表现出保护关联：CC motif趋化因子19 (CCL19) [OR 0.58；95% ci: 0.36-0.93；p = 0.024]，白细胞介素-10 (IL-10) [OR 0.41；95% ci: 0.23-0.72；p = 0.002]，白细胞介素- 17a (il - 17a) [OR 0.44；95% ci: 0.20-0.96；p = 0.040]，单核细胞趋化蛋白3 (MCP-3) [OR 0.51；95% ci: 0.29-0.89；p = 0.018]。相反，血浆中白细胞介素-33水平升高被认为是POI的危险因素[OR 2.83；95% ci: 1.23-6.50；p = 0.015]。结论：我们的研究结果表明特异性炎症细胞因子与发生POI的风险之间存在显著相关性。细胞因子如CCL19、IL-10、IL-17 A和MCP-3的负相关表明对POI有保护作用，而IL-33水平的正相关表明有潜在的不利影响。这些见解可以指导未来针对POI管理和预防的靶向免疫调节疗法的研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.