Genes regulating molecular and cellular functions in noninfectious nonallergic rhinitis.
BACKGROUND
Chronic noninfectious, nonallergic rhinitis (NINAR) is a complex syndrome with a principally unknown pathophysiology. New technology has made it possible to examine differentially expressed genes and according to network theory, genes connected by their function that might have key roles in the disease.


METHODS
Connectivity analysis was used to identify NINAR key genes. mRNA was extracted from nasal biopsies from 12 NINAR patients and 12 healthy volunteers. Microarrays were performed using Affymetrix chips with 54 613 genes. Data were analysed with the Ingenuity Pathway System for organization of genes into annotated biological functions and, thereafter, linking genes into networks due to their connectivity. The regulation of key genes was confirmed with reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
In all, 43 genes were differentially expressed. The functional analysis showed that these genes were primarily involved in cellular movement, haematological system development and immune response. Merging these functions, 10 genes were found to be shared. Network analysis generated three networks and two of these 'shared genes' in key positions, c-fos and cell division cycle 42 (Cdc42). These genes were upregulated in both the array and the RT-PCR analysis.


CONCLUSIONS
Ten genes were found to be of pathophysiological interest for NINAR and of these, c-fos and Cdc42 seemed to be of specific interest due to their ability to interact with other genes of interest within this context. Although the role of c-fos and Cdc42 in upper airway inflammation remains unknown, they might be used as potential disease markers.
Karolinska Institutet, Stockholm, Sweden.
L O
LO
Cardell
M
M
Andersson
A
A
Cervin
A
A
Davidsson
J
J
Hellgren
M
M
Holmström
L
L
Lundblad
P
P
Stierna
P
P
Stjärne
M
M
Adner
D000328:Adult; D000485:Allergens / Q000276:immunology; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012220:Rhinitis / Q000235:genetics* / Q000276:immunology; D012882:Skin Tests; D015854:Up-Regulation; D020764:cdc42 GTP-Binding Protein / Q000235:genetics
D000485:Allergens; D016760:Proto-Oncogene Proteins c-fos; D020764:cdc42 GTP-Binding Protein