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. STUDY DESIGN: Case-control genetic association study. SETTING: Tertiary-care university hospital. SUBJECTS AND 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 TOG 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). CONCLUSION: 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. (C) 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved.