c-MET pathway involvement in chronic rhinosinusitis: a genetic association analysis.
OBJECTIVE
The c-MET receptor and its ligand hepatocyte growth factor (HGF) has been shown to be overexpressed in tissue from chronic rhinosinusitis (CRS) patients with nasal polyps compared with that from controls. We assessed the genetic association of polymorphisms in the met proto-oncogene (MET) gene with CRS.


METHODS
Case-control genetic association study.


METHODS
Tertiary-care university hospital.


METHODS
A total of 206 unrelated Canadian patients with CRS and 196 control subjects were enrolled. Subjects were genotyped for 33 polymorphisms in the MET gene.


RESULTS
The allelic association analysis showed eight single nucleotide polymorphisms in the MET gene (rs38850, rs38855, rs38857, rs2237717, rs2402118, rs193688, rs1621, rs42336) with a statistically significant association with CRS. The rs38850 T allele showed the strongest association and the highest risk for CRS (P = 0.004; odds ratio 1.65, 95% confidence interval 1.18-2.32); the association did not reach statistical significance after adjustment for genomic control (P = 0.06). The haplotype TGG constructed of markers rs38850, rs38855, and rs38857 represented a risk haplotype, resulting in a P value of 0.003 that remained significant after correction for multiple testing (P = 0.018).


CONCLUSIONS
These data suggest that polymorphisms in the MET gene may play a role in the susceptibility to develop CRS. Study findings apply to patients with severe CRS unresponsive to surgery.
Castano
Roberto
R
Department of Otolaryngology, Hôpital Hôtel-Dieu de Montréal, Université de Montréal, Montréal, Québec, Canada. roberto.castano@mail.mcgill.ca
Bossé
Yohan
Y
Endam
Leandra Mfuna
LM
Filali-Mouhim
Abdelali
A
Desrosiers
Martin
M
D002908:Chronic Disease; D005260:Female; D055106:Genome-Wide Association Study; D017228:Hepatocyte Growth Factor / Q000032:analysis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000150:complications; D020641:Polymorphism, Single Nucleotide; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis*; D012220:Rhinitis / Q000150:complications / Q000235:genetics*; D012852:Sinusitis / Q000150:complications / Q000235:genetics*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met