Cui Jie, Zhao Yue-Chen, She Li-Zhen, Wang Tie-Jun
Department of Radiation Oncology, The Second Hospital of Jilin University, Changchun, Jilin, China.
Medicine (Baltimore). 2025 Feb 28;104(9):e41713. doi: 10.1097/MD.0000000000041713.
Previous studies have indicated that patients with uterine fibroids (UF) may have an elevated risk of cardiovascular disease (CVD), although the causal relationship between UF and CVD remains unclear. In this Mendelian randomization (MR) study, we aimed to investigate the causal association between genetic susceptibility to UF and the risk of developing CVD. We extracted summary statistics for single nucleotide polymorphisms associated with UF and 5 CVDs from multiple databases for further analysis. First, we used linkage disequilibrium score regression to assess the genetic correlation across the genome. Next, we performed univariate MR (UVMR), and to ensure the robustness of our results, we conducted sensitivity analyses using several methods. Additionally, we applied multivariable MR (MVMR) to adjust for potential confounders. The linkage disequilibrium score regression results showed that there was no genetic correlation between UF and coronary heart disease, myocardial infarction (MI), atrial fibrillation, heart failure, cardioembolic stroke (CES). The UVMR revealed a significant association between UF and CES (OR = 1.113, 95% confidence interval [CI]: 1.018-1.218, P = .019, PFDR = .047) and a suggestive causal relationship between UF and MI (OR = 0.943, 95% CI: 0.899-0.989, P = .015, PFDR = .075). In the MVMR analysis, after adjusting for a range of potential confounders, the causal relationships between UF and both CES (OR = 1.104, 95% CI = 1.012-1.205, P = .027) and MI (OR = 0.935, 95% CI = 0.882-0.992, P = .025) remained significant. Our study found that UF increase the risk of CES but decrease the risk of MI, providing a theoretical basis for further research into the underlying mechanisms.
先前的研究表明，子宫肌瘤（UF）患者患心血管疾病（CVD）的风险可能会升高，尽管UF与CVD之间的因果关系仍不清楚。在这项孟德尔随机化（MR）研究中，我们旨在调查UF的遗传易感性与发生CVD风险之间的因果关联。我们从多个数据库中提取了与UF和5种CVD相关的单核苷酸多态性的汇总统计数据，以进行进一步分析。首先，我们使用连锁不平衡评分回归来评估全基因组的遗传相关性。接下来，我们进行了单变量MR（UVMR），并且为确保结果的稳健性，我们使用多种方法进行了敏感性分析。此外，我们应用多变量MR（MVMR）来调整潜在的混杂因素。连锁不平衡评分回归结果显示，UF与冠心病、心肌梗死（MI）、心房颤动、心力衰竭、心源性栓塞性中风（CES）之间不存在遗传相关性。UVMR显示UF与CES之间存在显著关联（OR = 1.113，95%置信区间[CI]：1.018 - 1.218，P = 0.019，PFDR = 0.047），以及UF与MI之间存在提示性因果关系（OR = 0.943，95% CI：0.899 - 0.989，P = 0.015，PFDR = 0.075）。在MVMR分析中，在调整一系列潜在混杂因素后，UF与CES（OR = 1.104，95% CI = 1.012 - 1.205，P = 0.027）和MI（OR = 0.935，95% CI = 0.882 - 0.992，P = 0.025）之间的因果关系仍然显著。我们的研究发现，UF会增加CES的风险，但会降低MI的风险，为进一步研究潜在机制提供了理论依据。
