Epigenetics of chronic rhinosinusitis and the role of the eosinophil.
BACKGROUND
One theory for the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) involves aberration in the expression of genes that maintain the sinonasal innate immune system. We propose that the alteration in gene expression seen in CRSwNP is a result of oxidative byproducts of eosinophils. Activated eosinophils and neutrophils may lead to the production of hypobromous acid (HOBr) and hypochlorous acid (HOCL) and the posttranslational modification products 5-bromocytosine (5BrC) and 5-chlorocytosine (5ClC), respectively. 5BrC and 5ClC may cause aberrant methylation of cytosine during DNA replication and mimic the endogenous methylation signal associated with gene silencing. We propose to use gas chromatography-mass spectrometry (GC-MS) to identify the presence of 5BrC and 5ClC in CRSwNP patients.


METHODS
Patients with CRSwNP undergoing endoscopic sinus surgery were prospectively recruited into this study. Using GC-MS, tissue specimens were analyzed for the presence of 5BrC, 5ClC, and methylated cytosine.


RESULTS
Tissue specimens from 14 patients with CRSwNP and 3 normal controls were processed using GC-MS. CRSwNP specimens demonstrate elevated levels of 5BrC and 5ClC compared to normal controls.


CONCLUSIONS
Eosinophils, which are predominantly found in CRSwNP, may lead to DNA modification and gene silencing via 5BrC and aberrant methylation patterns and may help explain the pathogenesis of CRSwNP.
Department of Otolaryngology-Head and Neck Surgery, Loma Linda University, Loma Linda, CA 92354, USA. kristinseiberling@gmail.com
Kristin A
KA
Seiberling
Christopher A
CA
Church
Jason L
JL
Herring
Lawrence C
LC
Sowers
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001959:Bromates / Q000378:metabolism; D016022:Case-Control Studies; D002908:Chronic Disease; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism; D009298:Nasal Polyps / Q000235:genetics* / Q000378:metabolism; D012220:Rhinitis / Q000235:genetics* / Q000378:metabolism; D012852:Sinusitis / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
D001959:Bromates; C103182:5-bromocytosine; D006997:Hypochlorous Acid; D003596:Cytosine; C027664:hypobromous acid; C401182:5-chlorocytosine