LPCAT2 Methylation, a Novel Biomarker for the Severity of Cedar Pollen Allergic Rhinitis in Japan

Background Recently, the role of the epigenome in allergies has been receiving increasing attention. Although several genes that are methylated in relation to serum immunoglobulin E (IgE) concentration have been reported by epigenome-wide association studies, little is known about the DNA methylation sites associated with the symptoms and severity of cedar pollinosis (CP). Objective Our aim was to analyze the association between DNA methylation and the symptoms and severity of CP in peripheral blood mononuclear cells (PBMCs) and nasal mucosa scraping cells (NMSCs). Methods We recruited 70 participants during the cedar pollen dispersal season. IgE levels were measured by a fluorescence enzyme immunoassay. We analyzed DNA methylation of acyl-CoA thioesterase 7 ( ACOT7), mucin 4 ( MUC4), schlafen 12 ( SLFN12), lysophosphatidylcholine acyltransferase 2 ( LPCAT2), and interleukin-4 ( IL4) in PBMCs and NMSCs using bisulfite next-generation sequencing; the correlation of DNA methylation with non-specific IgE and cedar pollen-specific IgE levels in peripheral blood samples was also investigated. Symptom severity and DNA methylation were investigated in 15 untreated CP patients. Results Non-specific IgE levels showed a significant negative correlation with average IL4 methylation in PBMCs (r = −0.46, P < 0.0001) but not with methylation of ACOT7, MUC4, SLFN12, and LPCAT2. Cedar pollen-specific IgE levels showed a significant negative correlation with average IL4 and MUC4 methylation in PBMCs (r = −0.31, P = 0.01 and r = −0.241, P = 0.046, respectively) but not with methylation of ACOT7, SLFN12, and LPCAT2. The methylation of some genes in NMSCs was not significantly correlated with IgE levels. The mean methylation of LPCAT2 in NMSCs showed a decreasing trend with increasing severity of CP (P = 0.027). Conclusion LPCAT2 methylation in NMSCs may reflect the severity of CP and could be used as a novel biomarker to identify suitable treatment options for CP.