Vitamin D pathway regulatory genes encoding 1alpha-hydroxylase and 24-hydroxylase are dysregulated in sinonasal tissue during chronic rhinosinusitis
BACKGROUND: Vitamin 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). METHODS: A 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), 1alpha-hydroxylase (CYP27B1), and 24-hydroxylase (CYP24A1). Expression levels correlated with serum 25(OH)D [sum 25(OH)D2 and 25(OH)D3 ], the 22-item Sinonasal Outcome Test (SNOT-22), and Nasal Symptom Score (NSS). Separate analyses were performed for patients grouped by tissue eosinophilia. RESULTS: Thirty-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. CONCLUSIONS: The 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.
|ISBN||2042-6984 (Electronic) 2042-6976 (Linking)|
|Authors||Christensen, J. M.; Cheng, J.; Earls, P.; Gunton, J.; Sewell, W.; Sacks, R.; Harvey, R. J.|
|Responsible Garvan Author||Prof Bill Sewell|
|Publisher Name||International Forum of Allergy & Rhinology|
|URL link to publisher's version||https://www.ncbi.nlm.nih.gov/pubmed/27618536|