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双向孟德尔随机化研究的见解：评估循环炎症细胞因子对前列腺炎的影响。

Insights from bidirectional Mendelian randomization: Evaluating the influence of circulating inflammatory cytokines on prostatitis.

作者信息

Ma Jiaqi, Xu Lilei, Zhou Chuanlong, Shen Zhe, Zhu Kean, Lin Xianming

机构信息

Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.

Department of Acupuncture, Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.

出版信息

Medicine (Baltimore). 2025 May 9;104(19):e42438. doi: 10.1097/MD.0000000000042438.

DOI:10.1097/MD.0000000000042438
PMID:40355178
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12073858/
Abstract

Research on prostatitis has primarily focused on inflammatory cytokines in semen or prostatic secretions, with relatively few studies investigating circulating inflammatory cytokines. To explore the relationship between prostatitis and circulating inflammatory cytokines, this study employed bidirectional two-sample Mendelian randomization (MR) to assess the potential associations between prostatitis and 91 circulating inflammatory cytokines. We performed bidirectional MR to explore causal links between 91 circulating inflammatory cytokines and prostatitis. Data were sourced from 14,824 individuals of European ancestry and the Finngen database for prostatitis. The inverse variance-weighted (IVW) method was the primary tool, complemented by MR-Egger, weighted median, weighted mode, and MR-PRESSO to enhance result robustness. Heterogeneity and pleiotropy evaluations were conducted, and GO/KEGG enrichment analyses were used to explore the biological pathways linked to these inflammatory factors and prostatitis. The MR results revealed that Interleukin-10 receptor A (IL-10RA), Natural Killer Cell Receptor 2B4 (CD244), and urokinase-type plasminogen activator (uPA) were identified as risk factors for prostatitis (IVWIL-10RA: OR = 1.242, 95% CI: 1.043-1.478, P = .015; IVWCD244: OR = 1.143, 95% CI: 1.002-1.305, P = .047; IVWuPA: OR = 1.141, 95% CI: 1.009-1.290, P = .035). Conversely, Interleukin-12B (IL-12B) exhibited a protective effect against prostatitis (IVWIL-12B: OR = 0.909, 95% CI: 0.842-0.981, P = .014). Moreover, reverse MR analysis results indicate that prostatitis decreases plasma levels of chemokine (C-C motif) ligand 23 (CCL23), IL-5, and TNF-related activation-induced cytokine (TRANCE) (IVWCCL23: OR = 0.949, 95% CI: 0.906-0.993, P = .025; IVWIL-5: OR = 0.938, 95% CI: 0.890-0.988, P = .016; IVWTRANCE: OR = 0.947, 95% CI: 0.905-0.992, P = .021). This bidirectional MR study identified potential causal links between 7 circulating inflammatory cytokines and prostatitis, offering insights into its pathogenesis and potential targets for future therapies.

摘要

前列腺炎的研究主要集中在精液或前列腺分泌物中的炎性细胞因子，而对循环炎性细胞因子的研究相对较少。为了探索前列腺炎与循环炎性细胞因子之间的关系，本研究采用双向双样本孟德尔随机化（MR）方法，评估前列腺炎与91种循环炎性细胞因子之间的潜在关联。我们进行了双向MR，以探索91种循环炎性细胞因子与前列腺炎之间的因果联系。数据来源于14824名欧洲血统个体以及芬兰基因数据库中有关前列腺炎的数据。逆方差加权（IVW）方法是主要工具，辅以MR-Egger、加权中位数、加权众数和MR-PRESSO方法，以增强结果的稳健性。进行了异质性和多效性评估，并使用GO/KEGG富集分析来探索与这些炎性因子和前列腺炎相关的生物学途径。MR结果显示，白细胞介素-10受体A（IL-10RA）、自然杀伤细胞受体2B4（CD244）和尿激酶型纤溶酶原激活剂（uPA）被确定为前列腺炎的危险因素（IVW IL-10RA：优势比[OR]=1.242，95%置信区间[CI]：1.043-1.478，P=0.015；IVW CD244：OR=1.143，95%CI：1.002-1.305，P=0.047；IVW uPA：OR=1.141，95%CI：1.009-1.290，P=0.035）。相反，白细胞介素-12B（IL-12B）对前列腺炎具有保护作用（IVW IL-12B：OR=0.909，95%CI：0.842-0.981，P=0.014）。此外，反向MR分析结果表明，前列腺炎会降低趋化因子（C-C基序）配体23（CCL23）、IL-5和肿瘤坏死因子相关激活诱导细胞因子（TRANCE）的血浆水平（IVW CCL23：OR=0.949，95%CI：0.906-0.993，P=0.025；IVW IL-5：OR=0.938，95%CI：0.890-0.988，P=0.016；IVW TRANCE：OR=0.947，95%CI：0.905-0.992，P=0.021）。这项双向MR研究确定了7种循环炎性细胞因子与前列腺炎之间的潜在因果联系，为其发病机制及未来治疗的潜在靶点提供了见解。

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