降脂药物在哮喘和肺功能方面的再利用：遗传关联分析的证据。

Repurposing lipid-lowering drugs on asthma and lung function: evidence from a genetic association analysis.

机构信息

Department of Pediatrics, Xiangya Hospital, Central South University, Hunan, 410008, China.

Department of Orthopaedics, Xiangya Hospital, Central South University, Hunan, 410008, China.

出版信息

J Transl Med. 2024 Jul 3;22(1):615. doi: 10.1186/s12967-024-05359-5.

DOI:10.1186/s12967-024-05359-5

PMID:38961500

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11223406/

Abstract

OBJECTIVE

To explore the correlation between asthma risk and genetic variants affecting the expression or function of lipid-lowering drug targets.

METHODS

We conducted Mendelian randomization (MR) analyses using variants in several genes associated with lipid-lowering medication targets: HMGCR (statin target), PCSK9 (alirocumab target), NPC1L1 (ezetimibe target), APOB (mipomersen target), ANGPTL3 (evinacumab target), PPARA (fenofibrate target), and APOC3 (volanesorsen target), as well as LDLR and LPL. Our objective was to investigate the relationship between lipid-lowering drugs and asthma through MR. Finally, we assessed the efficacy and stability of the MR analysis using the MR Egger and inverse variance weighted (IVW) methods.

RESULTS

The elevated triglyceride (TG) levels associated with the APOC3, and LPL targets were found to increase asthma risk. Conversely, higher LDL-C levels driven by LDLR were found to decrease asthma risk. Additionally, LDL-C levels (driven by APOB, NPC1L1 and HMGCR targets) and TG levels (driven by the LPL target) were associated with improved lung function (FEV1/FVC). LDL-C levels driven by PCSK9 were associated with decreased lung function (FEV1/FVC).

CONCLUSION

In conclusion, our findings suggest a likely causal relationship between asthma and lipid-lowering drugs. Moreover, there is compelling evidence indicating that lipid-lowering therapies could play a crucial role in the future management of asthma.

摘要

目的

探讨影响降脂药物靶点表达或功能的遗传变异与哮喘风险之间的相关性。

方法

我们使用与降脂药物靶点相关的几个基因（HMGCR（他汀类药物靶点）、PCSK9（alirocumab 靶点）、NPC1L1（依折麦布靶点）、APOB（mipomersen 靶点）、ANGPTL3（evinacumab 靶点）、PPARA（fenofibrate 靶点）和 APOC3（volanesorsen 靶点）以及 LDLR 和 LPL）中的变异进行孟德尔随机化（MR）分析。我们的目的是通过 MR 研究降脂药物与哮喘之间的关系。最后，我们使用 MR Egger 和逆方差加权（IVW）方法评估 MR 分析的有效性和稳定性。

结果

发现与 APOC3 和 LPL 靶点相关的升高的甘油三酯（TG）水平与哮喘风险增加有关。相反，LDLR 驱动的 LDL-C 水平升高与哮喘风险降低有关。此外，LDL-C 水平（由 APOB、NPC1L1 和 HMGCR 靶点驱动）和 TG 水平（由 LPL 靶点驱动）与肺功能（FEV1/FVC）改善有关。PCSK9 驱动的 LDL-C 水平与肺功能（FEV1/FVC）降低有关。