Nasal mucosal gene expression in patients with allergic rhinitis with and without nasal polyps.
BACKGROUND
Nasal polyps are a common problem that is difficult to diagnose and treat, in part because the cause of nasal polyposis is unknown. Although information on the pathogenesis of polyposis is lacking, there are reports suggesting that a genetic predisposition underlies this disorder.


OBJECTIVE
We sought to better understand the basis of nasal polyposis associated with allergic rhinitis. We hypothesize that the expression of unique genes is associated with the nasal polyposis phenotype.


METHODS
We examined 12000 human genes transcribed in the nasal mucosa of patients with allergic rhinitis with and without nasal polyps. Biopsy specimens of the mucosa of patients with and without polyps were obtained after the patients refrained from the use of topical or systemic steroid therapy for 2 weeks.


RESULTS
Thirty-four genes were differentially expressed between the patient groups, including those for inflammatory molecules and putative growth factors. The greatest differential expression identified by the array analysis was for a group of genes associated with neoplasia, including mammaglobin, a gene transcribed 12-fold higher in patients with polyps compared with control patients with rhinitis alone. Quantitative RT-PCR confirmed this differential expression and documented that the number of mammaglobin mRNA copies is actually 64-fold greater in tissues of patients with polyps versus control patients. The specificity of mammaglobin protein expression was evaluated by means of immunohistochemistry, which showed specific staining in nasal polyp mucosal goblet cells only in patients with polyps.


CONCLUSIONS
These data suggest that nasal polyposis involves deregulated cell growth, using gene activation in some ways similar to a neoplasm. In addition, mammaglobin, a gene of unknown function associated with breast neoplasia, might be related to polyp growth.
Fritz
Stephen B
SB
Center of Biological Nanotechnology, Division of Allergy and Clinical Immunology, The University of Michigan Medical Center, Ann Arbor, MI 48103-0648, USA.
Terrell
Jeffrey E
JE
Conner
Edward R
ER
Kukowska-Latallo
Jolanta F
JF
Baker
James R
JR
D000328:Adult; D000368:Aged; D001706:Biopsy; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005914:Globins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D060785:Mammaglobin A; D008875:Middle Aged; D009185:Myelin Proteins; D009297:Nasal Mucosa / Q000378:metabolism*; D009298:Nasal Polyps / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011510:Proteolipids; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012221:Rhinitis, Allergic, Perennial / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D060765:Secretoglobins; D014598:Uteroglobin / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D060785:Mammaglobin A; D009185:Myelin Proteins; D009363:Neoplasm Proteins; D011510:Proteolipids; D012333:RNA, Messenger; C556448:SCGB2A2 protein, human; D060765:Secretoglobins; D012313:RNA; D005914:Globins; D014598:Uteroglobin