Association between methylation in nasal epithelial TSLP gene and chronic rhinosinusitis with nasal polyps
Association between methylation in nasal epithelial TSLP gene and chronic rhinosinusitis with nasal polyps
复制标题
鼻上皮TSLP基因甲基化与慢性鼻窦炎伴鼻息肉的相关性
DOI：
10.1186/s13223-019-0389-3
复制
发表时间：
2019-11-21
影响因子：
2.7
通讯作者：
Zhang, Luo
中科院分区：
文献类型：
--
作者：
Li, Jingyun;Jiao, Jian;Zhang, Luo
背景：本研究旨在探讨胸腺间质淋巴生成素(TSLP)基因异常甲基化与慢性鼻-鼻窦炎(CRS)发病机制的关系。方法对48例CRS鼻息肉患者(CRSwNP)、28例非鼻息肉CRS患者(CRSsNP)和21例健康体检者进行血清总IgE水平、嗅觉评分和鼻阻力测定。取CRSwNP患者鼻息肉、CRSsNP患者筛窦黏膜和对照组下鼻甲黏膜标本，分离纯化的原代人鼻上皮细胞(HNECs)。从每个受试者纯化的原代HNECs中提取基因组DNA，用Massarray EpiTYPER筛选TSLP基因选定区域的DNA甲基化比率。结果共分析了17个CpG单位，其中2个CpG单位(CpG3和22：23：24)在校正假发现率(FDR)后，CRSwNP患者的甲基化比率高于CRSsNP和对照组(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)、75Pa(r=0.24，P=0.04；r=0.24，P=0.036)和150pa(r=0.34，P=0.004；r=0.25，P=0.031)呈正相关。75 pA/150 pA的总鼻阻力或血清总IgE水平与CpG单位的甲基化比率均无相关性。结论TSLP基因的DNA甲基化增加可能与CRSwNP的发病机制有关；然而，这些发现需要在更大的多中心组研究中得到证实。
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.