Genetic Association of Lipids and Lipid-Lowering Drug Target Genes With Atopic Dermatitis: A Drug Target Mendelian...

Several observational studies have reported inconsistent associations between dyslipidaemia, stains use and atopic dermatitis (AD). Nevertheless, the available data on the effects of -C-lowering as well as TG-lowering drugs remain inconclusive and limited. The aim of this study was to evaluate the causal association of lipid traits and long-term use of lipid-lowering drugs on AD risk.

Drug-targeted Mendelian randomization analyses were performed in European ancestry. Pooled statistics on low-density lipoprotein cholesterol, triglyceride and AD were extracted from large genome-wide association studies datasets. Instrumental variables located in and around lipid-lowering target genes were used as proxies for therapeutic inhibition of these target genes. Inverse-variance-weighted approach was applied as the primary analysis.

We explored the role of seven lipid-lowering target genes in AD, among which genetically proxied Niemann-Pick C1-like 1 inhibition, a target of LDL-C-lowering drugs, was associated with an increased risk of AD (odds ratio, 3.03; 95% CI, 1.36-6.75; p = 0.007). This association was replicated in FinnGen cohort (odds ratio, 1.72; 95% CI, 1.09-2.72; p = 0.020). A series of sensitivity analyses confirmed the robustness of the estimates.

We found no genetic support for the repurposing of seven lipid-lowering drug targets for the prevention of AD. However, pharmacovigilance of AD risk in Niemann-Pick C1-like 1 inhibitor users may be warranted.