Circadian rhythmicity of sphingolipids in allergic asthma

Background: Genome-wide association studies have reproducibly linked the Orosomucoid-like 3 (ORMDL3) gene to risk of asthma. ORMDL3 regulates sphingolipid synthesis and is rhythmically expressed. There is mounting evidence supporting the role of sphingolipid metabolism in asthma pathogenesis. Since asthma is a highly rhythmic disease, we investigated whether serum sphingolipids vary by time of day in patients with and without asthma. Methods: Ten individuals with allergic asthma (AA) and 10 healthy non-smokers (HV) completed overnight visits. Blood samples were taken every 6 hours over 24hr. Targetted lipidomics analysis was performed using ultra performance liquid chromatography with tandem mass spectrometry. Results: Five ceramides (CER) at 4am and two at 4pm were significantly higher in AA than HV (p Conclusion: Sphingolipids in asthma acquire circadian rhythmicity. Further study is needed to gain mechanistic insight into the role of clock control in ORMDL3-sphingolipid pathway, which may lead to novel therapeutic approach in asthma.