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.
Highlights
Statins are one of the most commonly used drugs in the world which prevent cardiovascular diseases and reduce mortality[1]
None of the single nucleotide polymorphisms (SNPs) were associated with socioeconomic position, current smoking or alcohol consumed in the UK Biobank
We cannot exclude the possibility that genetically mimicked effects of statins via hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibition might increase the risk of asthma in East Asians
Summary
Statins are one of the most commonly used drugs in the world which prevent cardiovascular diseases and reduce mortality[1]. Statins have been suggested as a potential treatment for immune-related diseases, possibly due to their anti-inflammatory and immunomodulatory e ffects[5,6]. Trial evidence for statins treatment on other immune-related diseases is limited[6,9]. Observational studies of statins use and risk of developing auto-immune diseases are inconsistent[12–15]. Trial investigation of whether statins affect risk of auto-immune conditions is very limited. Few studies are sex-specific auto-immune conditions tend to be more common in women than m en[17], possibly because of hormone related effects on the immune system[18]. To assess the effects of statins via HMGCR inhibition on immune-related diseases, we used a Mendelian randomization (MR) study, i.e., instrumental variable analysis with genetic instruments, which takes advantage of genetic randomization at conception to obtain unconfounded estimates[21], here sex-. Sex-combined genome wide association study (GWAS) and sex-specific genetic summary statistics from the UK Biobank, with Biobank Japan used for replication
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