Vitamin D pathway regulatory genes encoding 1α-hydroxylase and 24-hydroxylase are dysregulated in sinonasal tissue during chronic rhinosinusitis.
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).



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), 1α-hydroxylase (CYP27B1), and 24-hydroxylase (CYP24A1). Expression levels correlated with serum 25(OH)D [sum 25(OH)D2and 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.



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.



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.
Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, NSW, Australia.
Jenna M
JM
Christensen
Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, NSW, Australia.
Jasmine
J
Cheng
Department of Anatomical Pathology, St Vincent's Hospital, Sydney, NSW, Australia.
Peter
P
Earls
Immunopathology Department, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Jenny
J
Gunton
Immunopathology Department, Garvan Institute of Medical Research, Sydney, NSW, Australia.
William
W
Sewell
Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.|Faculty of Medicine, University of Sydney, Sydney, NSW, Australia.
Raymond
R
Sacks
Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, NSW, Australia.|Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
Richard J
RJ
Harvey
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics*; D000328:Adult; D000368:Aged; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D002908:Chronic Disease; D000072467:Cytochrome P450 Family 2 / Q000235:genetics; D004724:Endoscopy; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006967:Hypersensitivity / Q000097:blood / Q000235:genetics / Q000601:surgery; D008297:Male; D008875:Middle Aged; D010256:Paranasal Sinuses / Q000378:metabolism / Q000601:surgery; D018167:Receptors, Calcitriol / Q000235:genetics; D012220:Rhinitis / Q000097:blood / Q000235:genetics* / Q000601:surgery; D012852:Sinusitis / Q000097:blood / Q000235:genetics* / Q000601:surgery; D014807:Vitamin D / Q000097:blood / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics*; D014815:Vitamins / Q000097:blood / Q000378:metabolism*
D018167:Receptors, Calcitriol; D014815:Vitamins; D014807:Vitamin D; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; C000600378:CYP27B1 protein, human
chronic rhinosinusitis; eosinophilic rhinosinusitis and nasal polyposis; paranasal sinuses; patient-reported outcome measure