Increased expression of serine palmitoyl transferase andORMDL3polymorphism are associated with eosinophilic inflammation and airflow limitation in aspirin-exacerbated respiratory disease

Background Patients with aspirin-exacerbated respiratory disease (AERD) are known to have poor clinical outcomes. The pathogenic mechanisms have not yet been completely understood. Objective We aimed to assess the involvement of thede-novosynthetic pathway of sphingolipid metabolism in patients with AERD compared to those with aspirin tolerant asthma (ATA). Methods A total of 63 patients with AERD and 79 patients with ATA were enrolled in this study. Analysis of mRNA expression of serine palmitoyl transferase, long-chain base subunit 2 (SPTLC2) and genotyping ofORMDL3SNP (rs7216389) was performed. Results Significantly higher levels of SPTLC2 mRNA expression were noted in patients with AERD, which showed significant positive correlations with peripheral/sputum eosinophil counts and urine LTE4(allP<0.05). The levels of SPTLC2 mRNA expression showed significant negative correlations with the level of FEV(1)and FEV1/FVC (P= 0.033,r= -0.274;P= 0.019,r= -0.299, respectively). Genotype frequencies ofORMDL3SNP (rs7216389) showed no significant differences between the AERD and ATA groups. Patients with AERD carrying the TT genotype ofORMDL3had significantly lower levels of FVC (%) and PC(20)methacholine than those carrying the CT or CC genotype (P= 0.026 andP= 0.030).