Investigating genetically mimicked effects of statins via HMGCR inhibition on immune-related diseases in men and women using Mendelian randomization

Abstract

Statins have been suggested as a potential treatment for immune-related diseases. Conversely, statins might trigger auto-immune conditions. To clarify the role of statins in allergic diseases and auto-immune diseases, we conducted a Mendelian randomization (MR) study. Using established genetic instruments to mimic statins via 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibition, we assessed the effects of statins on asthma, eczema, allergic rhinitis, rheumatoid arthritis (RA), psoriasis, type 1 diabetes, systemic lupus erythematosus (SLE), multiple sclerosis (MS), Crohn’s disease and ulcerative colitis in the largest available genome wide association studies (GWAS). Genetically mimicked effects of statins via HMGCR inhibition were not associated with any immune-related diseases in either study after correcting for multiple testing; however, they were positively associated with the risk of asthma in East Asians (odds ratio (OR) 2.05 per standard deviation (SD) decrease in low-density lipoprotein cholesterol (LDL-C), 95% confidence interval (CI) 1.20 to 3.52, p value 0.009). These associations did not differ by sex and were robust to sensitivity analysis. These findings suggested that genetically mimicked effects of statins via HMGCR inhibition have little effect on allergic diseases or auto-immune diseases. However, we cannot exclude the possibility that genetically mimicked effects of statins via HMGCR inhibition might increase the risk of asthma in East Asians.