Gene association of lipid traits, lipid-lowering drug target genes and endometriosis
Reproductive BioMedicine Online(2024)
摘要
Research Question
Does the observed correlation between dyslipidemia and endometriosis indicate bidirectional causal associations? Furthermore, is the prospect of utilizing lipid-lowering drugs to manage endometriosis a viable strategy?
Design
Bidirectional Mendelian Randomization (MR) is employed to investigate the causal association between lipid traits and endometriosis. Drug-target MR is utilized to explore potential drug-target genes for managing endometriosis. In cases where lipid-mediated effects via specific drug targets are significant, aggregate analyses, such as Summary-data-based Mendelian Randomization (SMR) and Colocalization methods, are introduced to validate the outcomes. Mediation analyses supplement these evaluations.
Results
Bidirectional MR results suggested that genetically predicted triglycerides (TG) (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.08-1.23), high-density lipoprotein cholesterol (HDL-C) (OR 0.87, 95% CI 0.81-0.94), low-density lipoprotein cholesterol (LDL-C) (OR 1.20, 95% CI 1.06-1.34) and apolipoprotein A (APOA) (OR 0.90, 95% CI 0.83-0.96) were causally associated with endometriosis. Reverse MR results revealed that genetically proxied endometriosis was causally associated with TG level (OR 1.02, 95% CI 1.01-1.02). In drug-target MR, genetic mimicry in proprotein convertase subtilisin/kexin type 9 (PCSK9) (OR1.40, 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) were significantly associated with the risk of endometriosis stages 1-2.
Conclusion
Our findings suggest a potential bidirectional causal association between endometriosis and dyslipidemia. Genetic mimicry of PCSK9, APOB, and ANGPTL3 is associated with the risk of early-stage endometriosis. The development of lipid-lowering drugs for treating endometriosis holds potential clinical interest.
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