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). 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. 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. 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.

中文翻译：

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鼻上皮TSLP基因甲基化与鼻息肉慢性鼻窦炎的相关性

本研究旨在确定胸腺基质淋巴细胞生成素 (TSLP) 基因座的异常 DNA 甲基化与慢性鼻窦炎 (CRS) 的发病机制之间是否存在任何关联。共有鼻息肉CRS患者（CRSwNP）48例，无鼻息肉CRS患者（CRSsNP）28例，对照组21例；并评估血清总 IgE 水平、嗅觉评分和鼻阻力。在手术期间从 CRSwNP 患者的鼻息肉、CRSsNP 患者的筛窦黏膜和对照受试者的下鼻甲 (IT) 黏膜中获取样本，并用于分离纯化的原代人鼻上皮细胞 (HNEC)。从每个受试者的纯化初级 HNEC 中提取基因组 DNA，并使用 MassARRAY EpiTYPER 筛选 TSLP 基因选定区域的 DNA 甲基化比率。共分析了 17 个 CpG 单位；其中两个 CpG 单位（CpG3 和 22:23:24）在校正错误发现率（FDR）后，与 CRSsNP 和对照受试者相比，CRSwNP 患者的甲基化比率增加（Q < 0.1）。CpG3 和 CpG22:23:24 单位的甲基化比率与嗅觉评分 (r = 0.41, P = 0.0001; r = 0.25, P = 0.021) 和 75 Pa 时的单侧鼻阻力 (r = 0.24, P = 0.04；r = 0.24，P = 0.036）和 150 Pa（r = 0.34，P = 0.004；r = 0.25，P = 0.031）。75 Pa/150 Pa 的总鼻阻力或血清总 IgE 水平与任一 CpG 单位的甲基化比率均不相关。TSLP 基因座 DNA 甲基化增加可能与 CRSwNP 发病机制有关；然而，这些发现需要在更大的多中心小组研究中得到证实。