LPCAT2 Methylation, a Novel Biomarker for the Severity of Cedar Pollen Allergic Rhinitis in Japan. Issue 5 (September 2021) - Watanabe, Hiroyuki
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.