Wei Yunfang, Zhao Xianlei, Li Linxia
Department of Obstetrics & Gynecology, Shanghai Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, People's Republic of China.
School of Life Sciences, Fudan University, Shanghai, 200438, People's Republic of China.
Immunotargets Ther. 2024 Nov 1;13:585-593. doi: 10.2147/ITT.S486139. eCollection 2024.
Endometriosis is a complex gynecological condition in which endometrial fragments are implanted outside the uterus, causing pain and infertility. Although immune mediators play a vital role in endometriosis, their exact etiology remains elusive. Using Mendelian randomization (MR), this study aimed to assess the causal relationship between inflammatory proteins and endometriosis.
Genetic variants associated with inflammatory proteins were filtered from a genome-wide protein quantitative trait locus study under stringent thresholds. These variants were used as instrumental variables (IVs) to evaluate the causal effects of these inflammatory proteins on endometriosis. A two-sample MR analysis was performed with endometriosis from the UK Biobank as the outcome, and a sensitivity analysis was performed to mitigate potential confounding factors. Analyses were replicated in an independent endometriosis cohort from the FinnGen, followed by a meta-analysis of MR results from both cohorts. Finally, we assessed the causality between inflammatory proteins and the endometriosis subtypes.
Independent MR analysis revealed that the genetically higher levels of CXCL5 were linked to a lower chance of having endometriosis. The causal link remained significant in the meta-analysis. Furthermore, the causality of CXCL5 expression has been identified in ovarian and pelvic peritoneal endometriosis.
Our MR analysis indicated that CXCL5 was associated with a decreased risk of endometriosis, suggesting that CXCL5 might have a protective effect against endometriosis. This enhances our understanding of the involvement of chemokines in endometriosis pathology and provides insights for future studies to explore the detailed mechanisms underlying CXCL5 in endometriosis.
子宫内膜异位症是一种复杂的妇科疾病，其中子宫内膜碎片植入子宫外，导致疼痛和不孕。尽管免疫介质在子宫内膜异位症中起着至关重要的作用，但其确切病因仍不清楚。本研究采用孟德尔随机化（MR）方法，旨在评估炎症蛋白与子宫内膜异位症之间的因果关系。
在严格的阈值下，从全基因组蛋白质定量性状位点研究中筛选出与炎症蛋白相关的基因变异。这些变异被用作工具变量（IVs），以评估这些炎症蛋白对子宫内膜异位症的因果效应。以英国生物银行的子宫内膜异位症为结局进行两样本MR分析，并进行敏感性分析以减轻潜在的混杂因素。在来自芬兰基因库的独立子宫内膜异位症队列中重复分析，然后对两个队列的MR结果进行荟萃分析。最后，我们评估了炎症蛋白与子宫内膜异位症亚型之间的因果关系。
独立的MR分析显示，基因水平上较高的CXCL5与患子宫内膜异位症的几率较低有关。在荟萃分析中，这种因果关系仍然显著。此外，CXCL5表达的因果关系已在卵巢和盆腔腹膜子宫内膜异位症中得到证实。
我们的MR分析表明，CXCL5与子宫内膜异位症风险降低有关，提示CXCL5可能对子宫内膜异位症具有保护作用。这增强了我们对趋化因子参与子宫内膜异位症病理过程的理解，并为未来研究探索CXCL5在子宫内膜异位症中的详细机制提供了见解。
