Association Between PCSK9 Inhibitors and Autoimmune Diseases:A Mendelian Randomization Study
OBJECTIVE Several observational studies suggest a possible link between PCSK9 inhibitors and autoimmune diseases.However,inferring causality from these studies can be influenced by residual confounding effects,reverse causation,and bias.To investigate the potential causal effect of proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors on autoimmune disease(Crohn's disease,Psoriasis,Rheumatoid arthritis,Systemic lupus erythematosus,Type 1 Diabetes and Ulcerative colitis),we performed a Mendelian randomization(MR)-based study.METHODS Selecting genetic variants(single nucleotide polymorphisms)near or within drug target genes associated with low-density lipoprotein as instrumental variables,and applying MR methods to analyze data from genome-wide association studies of European ancestry.The inverse-variance weighted(IVW)-MR approach was used as the main analysis method to conduct sensitivity analysis and test the robustness of the results.RESULTS The IVW-MR analysis revealed significant evidence for an association between PCSK9-mediated LDL-C and the risk of psoriasis(OR=1.264,95％CI=1.117-1.431,P＜0.01),rheumatoid arthritis(OR=1.151,95％CI=1.032-1.284,P=0.011),systemic lupus erythematosus(OR=1.740,95％CI=1.227-2.468,P＜0.01).CONCLUSION Our findings support a potential therapeutic effect of PCSK9 inhibitors on psoriasis,rheumatoid arthritis and systemic lupus erythematosus.
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