Lipids, Lipid-Lowering Drug Target Genes, and COPD Risk: A Mendelian Randomization Study

Some studies suggest that statins could reduce the risk of chronic obstructive pulmonary disease (COPD), but it is unclear if this effect is related to their lipid-lowering properties. The causal link between serum lipid levels and COPD risk remains uncertain. This study aims to clarify this potential causal relationship and evaluate the impact of lipid-lowering drug target genes on COPD.

Mendelian randomization (MR) was used to investigate causal associations between lipid levels, lipid-lowering drug target genes, and COPD risk. Data were obtained from publicly available genome-wide association study databases. The inverse variance weighted method was the primary statistical approach for evaluating causal effects, complemented by various sensitivity analyses.

MR analysis demonstrated a causal relationship between low-density lipoprotein cholesterol (LDL-C) and a reduced risk of COPD (odds ratio [OR]=0.90, 95% confidence interval [CI]=0.85-0.95, P=1.50×10⁻⁴). Causal relationships were also identified for 2 lipid-lowering drug target genes, HMGCR (OR=0.63, 95%CI=0.54-0.75, P=4.92×10⁻⁸) and PCSK9 (OR=0.87, 95%CI=0.80-0.95, P=0.001), with a reduced COPD risk. Although MR analysis indicated a potential causal relationship between LPL (OR=0.86, 95%CI=0.79-0.94, P=6.37×10⁻⁴) and reduced COPD risk, colocalization analysis did not support this finding. No associations were observed between other lipid traits, lipid-lowering drug target genes, and COPD.

This study genetically identified causal relationships between serum LDL-C levels, the 2 coding genes HMGCR and PCSK9, and a reduced risk of COPD. These findings suggest that the protective effect of statins on COPD may occur independently of their lipid-lowering function. Further clinical validation is needed to confirm this hypothesis.