Background: This study was performed to determine whether there was any association between abnormal DNA\nmethylation of a thymic stromal lymphopoietin (TSLP) locus and pathogenesis of chronic rhinosinusitis (CRS).\nMethods: A total of 48 CRS patients with nasal polyps (CRSwNP), 28 CRS patients without nasal polyps (CRSsNP) and\n21 control subjects were enrolled into the study; and evaluated for serum total IgE level, olfactory score and nasal\nresistance. Samples were obtained from nasal polyps of CRSwNP patients, ethmoid mucosae of CRSsNP patients\nand inferior turbinate (IT) mucosa of control subjects during surgery, and used to isolate purified primary human\nnasal epithelial cells (HNECs). Genomic DNA was extracted from purified primary HNECs of each subject and DNA\nmethylation ratios for a selected region of the TSLP gene were screened the using MassARRAY EpiTYPER.\nResults: A total of 17 CpG units were analyzed; of which two CpG units (CpG3 and 22:23:24) had increased\nmethylation ratios in the CRSwNP patients compared to the CRSsNP and control subjects after correction for false\ndiscovery rate (FDR) (Q < 0.1). The methylation ratios at both CpG3 and CpG22:23:24 units were positively correlated\nwith 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;\nr = 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\ntotal IgE levels were not correlated with the methylation ratios at either CpG unit.\nConclusions: Increased DNA methylation at the TSLP locus is likely to be associated with CRSwNP pathogenesis;\nhowever these findings need to be confirmed in larger multicentre group studies.
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