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Non-Causal Association of Sepsis with PCSK9 Inhibitor and HMGCR Inhibitor: A Drug Target Mendelian Randomization
17 Pages Posted: 6 Nov 2023
More...Abstract
Background: The inhibitors of the Proprotein convertase subtilis kexin 9 (PCSK9) and 3-Hydroxy-3-methylglutaryl-assisted enzyme A reductase (HMGCR) have significant cholesterol-lowering effects, and are potent agents in reducing the incidence of cardiovascular disease. Currently, some studies have reported that it is also strongly and positively associated with the incidence of sepsis. However, we doubt their relationship.
Objective: We attempted to evaluate the association between PCSK9 Inhibitor and HMGCR inhibitor and sepsis by mendelian randomization (MR)method.
Methods: We extracted SNPs for PCSK9 and HMGCR from the genome-wide association study (GWAS) database for European ancestry. Coronary heart disease (CHD) was used as a positive control, and we took a drug-targeted MR analysis to analyze the causal relationship between them. Finally, we performed a meta-analysis of the preliminary results. IVW method results from 5 datasets suggest that HMGCR inhibitors do not reduce the risk of sepsis. But 3 datasets suggest that HMGCR inhibitors can reduce the risk of sepsis.
Results: We failed to find significant association between PCSK9 Inhibitor and HMGCR Inhibitor and sepsis. IVW method results from 8 datasets suggest that PCSK9 inhibitors do not reduce the risk of sepsis. Meta-analysis showed that PCSK9 inhibitors [I2=5%, (OR [95%] = 1.05 [0.99 to 1.12], p=0.39)] and HMGCR inhibitors[I2=74%, (OR [95%] = 0.96 [0.73 to 1.26], p<0.01)] had no significant effect on sepsis.
Conclusion: This study does not support the association of PCSK9 Inhibitor and HMGCR Inhibitor with sepsis.
Funding: This work was supported by the Hebei Natural Science Foundation (No.H2022423369) and the Hebei Provincial Government Funding the Training of Excellent Clinical Medical Talents and Basic Research Projects (No.2016034829).
Declaration of Interest: The authors declare that there is no conflict of interest regarding the publication of this paper.
Keywords: PCSK9 inhibitor, HMGCR inhibitor, sepsis, Mendelian randomization, drug target, meta analysis
Suggested Citation: Suggested Citation