Association between methylation in nasal epithelial TSLP gene and chronic rhinosinusitis with nasal polyps

BACKGROUND: This study was performed to determine whether there was any association between abnormal DNA methylation of a thymic stromal lymphopoietin (TSLP) locus and pathogenesis of chronic rhinosinusitis (CRS). METHODS: A total of 48 CRS patients with nasal polyps (CRSwNP), 28 CRS patients without nasal polyps (CRSsNP) and 21 control subjects were enrolled into the study; and evaluated for serum total IgE level, olfactory score and nasal resistance. Samples were obtained from nasal polyps of CRSwNP patients, ethmoid mucosae of CRSsNP patients and inferior turbinate (IT) mucosa of control subjects during surgery, and used to isolate purified primary human nasal epithelial cells (HNECs). Genomic DNA was extracted from purified primary HNECs of each subject and DNA methylation ratios for a selected region of the TSLP gene were screened the using MassARRAY EpiTYPER. RESULTS: A total of 17 CpG units were analyzed; of which two CpG units (CpG3 and 22:23:24) had increased methylation ratios in the CRSwNP patients compared to the CRSsNP and control subjects after correction for false discovery rate (FDR) (Q < 0.1). The methylation ratios at both CpG3 and CpG22:23:24 units were positively correlated with olfactory score (r = 0.41, P = 0.0001; r = 0.25, P = 0.021) and unilateral nasal resistance at 75 Pa (r = 0.24, P = 0.04; r = 0.24, P = 0.036) and 150 Pa (r = 0.34, P = 0.004; r = 0.25, P = 0.031). Total nasal resistance at 75 Pa/150 Pa or serum total IgE levels were not correlated with the methylation ratios at either CpG unit. CONCLUSIONS: Increased DNA methylation at the TSLP locus is likely to be associated with CRSwNP pathogenesis; however these findings need to be confirmed in larger multicentre group studies.