Mendelian randomization-based observational cohort study on drug targets: Impact of antihypertensive and lipid-lowering therapies on inflammatory cytokines

This study assesses the causal effects of antihypertensive and lipid-lowering drugs on inflammatory cytokines using a Mendelian randomization (MR) approach. We conducted a drug-targeted MR analysis using data from large-scale genome-wide association studies and eQTL datasets. SNPs near drug target genes served as instrumental variables to investigate the impact of antihypertensive (angiotensin-converting enzyme inhibitors [ACEIs], ARBs) and lipid-lowering drugs (HMGCR inhibitors, proprotein convertase subtilisin/Kexin type 9 [PCSK9] inhibitors, Niemann-Pick C1-like 1 inhibitors) on inflammatory cytokines. Sensitivity analyses, including leave-one-out and MR-Egger tests, were performed to confirm the robustness of the findings. ACEIs were associated with decreased levels of IL-1β, TNF-α, and CRP. ARBs did not show significant effects on inflammatory cytokines. HMGCR inhibitors significantly reduced MCP-1, MIP-1β, TNF-α, and IFN-γ, while PCSK9 inhibitors were linked to reductions in IL-1β and IL-6. Sensitivity analyses supported the reliability of these findings. The study demonstrated distinct anti-inflammatory effects of ACEIs, HMGCR inhibitors, and PCSK9 inhibitors. These findings support the potential use of these drugs to mitigate inflammation-related complications in patients with chronic conditions.