摘要
Background:Chronic obstructive pulmonary disease(COPD)is a prevalent respiratory ailment that has risen to become the foremost cause of mortality globally,and statins are a widely used class of lipid-modifying drugs.Data from some observational studies suggest an association between statins use and COPD.Objectives:The main objective of this study was to investigate whether lipids and apolipoproteins are bidirectionally causally associated with COPD at the genetic level using a Mendelian randomization(MR)design,and to determine the potential role of circulating inflammatory proteins as mediators in this association.Methods:The publicly available Genome-Wide Association Study(GWAS)database was utilised for the purposes of the analysis.The data on high-density lipoprotein(HDL-C),low-density lipoprotein(LDL-C),triglycerides(TG),apolipoprotein A-1(ApoA1),and apolipoprotein B(ApoB)were obtained from the UK BioBank,while the COPD dataset was obtained from the FinnGen BioBank R11(number of cases:21,617,number of controls:372,627).Furthermore,data were gathered on genetic variants linked to inflammatory processes,encompassing 91 circulating inflammatory proteins(n=14,823 individuals).A two-sample MR study was conducted using these data to assess the association between HDL-C,LDL-C,TG,ApoA1,and ApoB with the risk of COPD.Furthermore,in order to investigate the potential mediating influence of inflammatory factor alterations between lipids and COPD,a two-step Mendelian randomization(MR)mediation analysis was conducted.Results:The forward MR methods identified two lipids that were found to have a causal relationship with the development of COPD.An elevated level of LDL-C and ApoB was found to be associated with a diminished risk of COPD.Furthermore,the researchers identified circulating inflammatory factors that were determined to be the causal agents in the development of COPD.Mediation analysis indicated that the inflammatory protein S100-A12 may act as a mediator between the LDL-C and COPD pathways.Conclusion:The present MR study provides genetic evidence for a causal relationship between lipids and apolipoproteins and COPD,as well as identifying the inflammatory protein S100-A12 as a potential mediator of the COPD association.The findings offer valuable insights into the mechanistic studies of statins for COPD and potential targets for disease intervention and treatment.
基金
supported by the Key Support Project of Regional Innovation and Development Joint Fund of National Natural Science Foundation of China(U20A20398)
the National Natural Science Foundation of China(82104454,82374399)
the Clinical Medical Research Transformation Project of Anhui Province(202304295107020111)
the Natural Science Research Key Project of Anhui Provincial Department of Education(KJ2021A0542).
