Department of Reproductive Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.
Department of Reproductive Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China; The First College of Clinical Medical, Nanjing University of Chinese Medicine, Nanjing, China.
Reprod Biomed Online. 2024 Jul;49(1):103856. doi: 10.1016/j.rbmo.2024.103856. Epub 2024 Feb 2.
Does the observed correlation between dyslipidaemia and endometriosis indicate a bidirectional causal association?
Bidirectional Mendelian randomization was used to investigate the causal association between lipid traits and endometriosis. Drug-target Mendelian randomization was used to explore potential drug-target genes for managing endometriosis. In cases where lipid-mediated effects via specific drug targets were significant, aggregate analyses, such as summary-data-based Mendelian randomization and colocalization methods, were introduced to validate the outcomes. Mediation analyses supplemented these evaluations.
The bidirectional Mendelian randomization results suggested that genetically predicted triglyceride (OR 1.15, 95% CI 1.08-1.23), high-density lipoprotein cholesterol (OR 0.87, 95% CI 0.81-0.94), low-density lipoprotein cholesterol (OR 1.20, 95% CI 1.06-1.34) and apolipoprotein A (OR 0.90, 95% CI 0.83-0.96) concentrations were causally associated with endometriosis. Reverse Mendelian randomization results revealed that genetically proxied endometriosis was causally associated with triglyceride concentration (OR 1.02, 95% CI 1.01-1.02). In drug-target Mendelian randomization, genetic mimicry in proprotein convertase subtilisin/kexin type 9 (PCSK9) (OR 1.40, 95% CI 1.13-1.72), apolipoprotein B (APOB) (OR 1.49, 95% CI 1.21-1.86) and angiopoietin-related protein 3 (ANGPTL3) (OR 1.57, 95% CI 1.14-2.16) was significantly associated with the risk of endometriosis stages 1-2.
There is a potential bidirectional causal association between endometriosis and dyslipidaemia. Genetic mimicry of PCSK9, APOB and ANGPTL3 is associated with the risk of early-stage endometriosis. The development of lipid-lowering drugs to treat endometriosis is of potential clinical interest.
血脂异常与子宫内膜异位症之间的观察到的相关性是否表明存在双向因果关联？
采用双向孟德尔随机化来研究脂质特征与子宫内膜异位症之间的因果关系。药物-靶标孟德尔随机化用于探索治疗子宫内膜异位症的潜在药物-靶标基因。在特定药物靶标通过脂质介导的影响具有统计学意义的情况下，引入汇总数据分析的孟德尔随机化和共定位方法等进行汇总分析，以验证结果。中介分析补充了这些评估。
双向孟德尔随机化结果表明，遗传预测的甘油三酯（OR 1.15，95%CI 1.08-1.23）、高密度脂蛋白胆固醇（OR 0.87，95%CI 0.81-0.94）、低密度脂蛋白胆固醇（OR 1.20，95%CI 1.06-1.34）和载脂蛋白 A（OR 0.90，95%CI 0.83-0.96）浓度与子宫内膜异位症存在因果关系。反向孟德尔随机化结果显示，遗传上接近的子宫内膜异位症与甘油三酯浓度存在因果关系（OR 1.02，95%CI 1.01-1.02）。在药物-靶标孟德尔随机化中，前蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 9（PCSK9）（OR 1.40，95%CI 1.13-1.72）、载脂蛋白 B（APOB）（OR 1.49，95%CI 1.21-1.86）和血管生成素相关蛋白 3（ANGPTL3）（OR 1.57，95%CI 1.14-2.16）的遗传模拟与 1 期至 2 期子宫内膜异位症的发病风险显著相关。
子宫内膜异位症与血脂异常之间存在潜在的双向因果关系。PCSK9、APOB 和 ANGPTL3 的遗传模拟与早期子宫内膜异位症的发病风险相关。开发降血脂药物治疗子宫内膜异位症具有潜在的临床意义。
