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已发表论文
91种循环炎症蛋白水平与卵巢相关疾病的关联：双向孟德尔随机化研究
Received 10 September 2025
Accepted for publication 3 December 2025
Published 9 December 2025 Volume 2025:17 Pages 5315—5327
DOI https://doi.org/10.2147/IJWH.S566694
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Everett Magann
Jiahui Qu, Liying Zhang
Department of Obstetrics and Gynecology, the Second Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China
Correspondence: Liying Zhang, Department of Obstetrics and Gynecology, the Second Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China, Email zitarobitaillez@gmail.com
Background: Inflammatory proteins play a pivotal role in the pathogenesis of ovarian diseases, although the underlying mechanisms remain poorly understood. The aim of this study is to investigate the association between circulating markers of inflammation and ovarian diseases.
Methods: A two-sample bidirectional Mendelian randomization (MR) approach was employed, utilizing publicly available genetic databases to examine the relationship between 91 circulating inflammatory markers and six ovarian diseases. The primary analysis utilized the inverse variance weighting (IVW) method, with additional sensitivity analyses, including heterogeneity and pleiotropy tests, to assess the robustness of the findings.
Results: Specific inflammatory markers were found to be associated with ovarian diseases and to exhibit causal relationships. Ovarian cysts were linked to CCL4 and other proteins, showing a positive causal relationship with NT-3. Polycystic ovary syndrome (PCOS) was associated with IL-6 and other markers, with a positive causal relationship to IL-17C. Ovarian dysfunction was associated with IL-6 and other markers, while primary ovarian failure was linked to IL-33. Benign ovarian neoplasms were associated with CCL28 and other proteins, showing a positive causal relationship with FGF-19 and negative causal relationships with FGF-5 and NT-3. Malignant ovarian neoplasms were associated with CCL20 and other markers.
Discussion: This study clarifies the causal relationships between circulating inflammatory markers and ovarian diseases, providing a crucial foundation for future translational research and clinical applications.
Keywords: Mendelian randomization, circulating inflammatory protein, ovarian-related diseases, polycystic ovary syndrome, ovarian neoplasm
Department of Obstetrics and Gynecology, the Second Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China
Correspondence: Liying Zhang, Department of Obstetrics and Gynecology, the Second Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China, Email zitarobitaillez@gmail.com
Background: Inflammatory proteins play a pivotal role in the pathogenesis of ovarian diseases, although the underlying mechanisms remain poorly understood. The aim of this study is to investigate the association between circulating markers of inflammation and ovarian diseases.
Methods: A two-sample bidirectional Mendelian randomization (MR) approach was employed, utilizing publicly available genetic databases to examine the relationship between 91 circulating inflammatory markers and six ovarian diseases. The primary analysis utilized the inverse variance weighting (IVW) method, with additional sensitivity analyses, including heterogeneity and pleiotropy tests, to assess the robustness of the findings.
Results: Specific inflammatory markers were found to be associated with ovarian diseases and to exhibit causal relationships. Ovarian cysts were linked to CCL4 and other proteins, showing a positive causal relationship with NT-3. Polycystic ovary syndrome (PCOS) was associated with IL-6 and other markers, with a positive causal relationship to IL-17C. Ovarian dysfunction was associated with IL-6 and other markers, while primary ovarian failure was linked to IL-33. Benign ovarian neoplasms were associated with CCL28 and other proteins, showing a positive causal relationship with FGF-19 and negative causal relationships with FGF-5 and NT-3. Malignant ovarian neoplasms were associated with CCL20 and other markers.
Discussion: This study clarifies the causal relationships between circulating inflammatory markers and ovarian diseases, providing a crucial foundation for future translational research and clinical applications.
Keywords: Mendelian randomization, circulating inflammatory protein, ovarian-related diseases, polycystic ovary syndrome, ovarian neoplasm