Vitamin D pathway regulatory genes encoding 1-hydroxylase and 24-hydroxylase are dysregulated in sinonasal tissue during chronic rhinosinusitis
Vitamin D pathway regulatory genes encoding 1-hydroxylase and 24-hydroxylase are dysregulated in sinonasal tissue during chronic rhinosinusitis
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DOI：
10.1002/alr.21852
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发表时间：
2017-02-01
影响因子：
6.4
通讯作者：
Harvey, Richard J.
中科院分区：
文献类型：
--
作者：
Christensen, Jenna M.;Cheng, Jasmine;Harvey, Richard J.
背景维生素D缺乏与许多炎症性呼吸道疾病有关。然而，血清维生素D浓度可能不能反映组织特异性的可用性。在这项研究中，我们试图评估慢性鼻窦炎（CRS）中维生素D调节所必需的基因的局部表达。MethodsA横断面研究进行了内窥镜鼻窦手术的成人患者。患者定义为CRS伴息肉（CRSwNP）或不伴息肉（CRSsNP），或正常鼻窦粘膜。使用定量聚合酶链反应评估窦粘膜活检，以确定编码维生素D受体（VDR）、25-羟化酶（CYP 2 R1）、1-羟化酶（CYP 27 B1）和24-羟化酶（CYP 24 A1）的基因表达。表达水平与血清25（OH）D [25（OH）D（2）和25（OH）D-3之和]、22项鼻窦结局测试（SNOT-22）和鼻症状评分（NSS）相关。单独进行分析，组织嗜酸性粒细胞增多症分组的患者进行了评估（年龄49.47 - 18.14岁，48.4%的女性），包括8 CRSsNP，10 CRSwNP，和13个控制。与对照组相比，CRSsNP和CRSwNP粘膜表现出降低的CYP 27 B1（0.0437 [四分位距（IQR）0.0999] vs 0.3260 [IQR 2.9384] vs 0.6557 [IQR 1.1005]，p = 0.039），而CYP 24 A1上调（0.8522 [IQR 1.3170] vs 1.2239 [IQR 4.4197] vs 0.1076 [IQR 0.1791]，p = 0.025）。CYP 24 A1在非嗜酸性粒细胞CRS和嗜酸性粒细胞CRS中均上调（1.1337 [IQR 2.3790] vs 0.9555 [IQR 3.2811] vs 0.1076 [IQR 0.1791]，p = 0.033）。NSS与CYP 2 R1之间存在显著相关性（r =-0.432，p = 0.022），CYP24A1（r = 0.420，P = 0.026），和VDR（r = 0.425，p = 0.024），尽管与血清25（OH）结论CRS时鼻窦组织中维生素D的局部调节可能与血清25（OH）D水平无关。维生素D可能在多个水平上失调，观察到代谢基因CYP 27 B1的转录减少和分解代谢基因CYP 24 A1的转录增加。
BackgroundVitamin D deficiency is associated with many inflammatory respiratory disease states. However, serum vitamin D concentrations may not reflect tissue-specific availability. In this study we sought to assess the local expression of genes essential in vitamin D regulation in chronic rhinosinusitis (CRS).MethodsA cross-sectional study of adult patients undergoing endoscopic sinus surgery was performed. Patients were defined as having CRS with polyps (CRSwNP) or without polyps (CRSsNP), or normal sinus mucosa. Sinus mucosal biopsies were assessed using quantitative polymerase chain reaction to determine expression of genes encoding the vitamin D receptor (VDR), 25-hydroxylase (CYP2R1), 1-hydroxylase (CYP27B1), and 24-hydroxylase (CYP24A1). Expression levels correlated with serum 25(OH)D [sum 25(OH)D(2)and 25(OH)D-3], the 22-item Sinonasal Outcome Test (SNOT-22), and Nasal Symptom Score (NSS). Separate analyses were performed for patients grouped by tissue eosinophilia.ResultsThirty-one patients were assessed (age 49.47 18.14 years, 48.4% female), including 8 CRSsNP, 10 CRSwNP, and 13 controls. CRSsNP and CRSwNP mucosa exhibited decreased CYP27B1 compared with controls (0.0437 [Interquartile range (IQR) 0.0999] vs 0.3260 [IQR 2.9384] vs 0.6557 [IQR 1.1005], p = 0.039), whereas CYP24A1 was upregulated (0.8522 [IQR 1.3170] vs 1.2239 [IQR 4.4197] vs 0.1076 [IQR 0.1791], p = 0.025). CYP24A1 was upregulated in both non-eosinophilic CRS and eosinophilic CRS (1.1337 [IQR 2.3790] vs 0.9555 [IQR 3.2811] vs 0.1076 [IQR 0.1791], p = 0.033). Significant correlations were observed between NSS and CYP2R1 (r = -0.432, p = 0.022), CYP24A1 (r = 0.420, P = 0.026), and VDR (r = 0.425, p = 0.024), although no correlations with serum 25(OH)D were observed.ConclusionsThe local regulation of vitamin D in sinonasal tissue during CRS may be independent of serum 25(OH)D levels. Vitamin D may be dysregulated at multiple levels, with decreased transcription of the metabolic gene CYP27B1 and increased transcription of the catabolic gene CYP24A1 observed.