Relationship between neurokinin 2 receptor gene polymorphisms and serum vascular endothelial growth factor levels in patients with toluene diisocyanate-induced asthma

Background: Among the various pathogenic mechanisms of toluene diisocyanate (TDI)-induced asthma, a contribution from neurogenic inflammation has been suggested. Objective: To evaluate neurokinin 2 receptor (NK2R) gene polymorphisms in association with the clinical phenotype of TDI-induced asthma, 70 TDI-induced occupational asthma (TDI-OA)patients, 59 asymptomatic exposed controls (AEC), and 93 unexposed healthy controls (NC) were enrolled in the study. Methods: Two single-nucleotide polymorphisms (SNPs) of NK2R, 7853G>A (Gly231Glu) and 11 424G>A (Arg375His), were genotyped using a single base extension method. The levels of PC₂₀ methacholine, specific IgE and IgG to TDI-human serum albumin conjugate, and serum vascular endothelial growth factor (VEGF), matrix metalloproteinase-9, and TGF-β1 were compared according to the NK2R genotypes of the subjects with TDI-OA and AEC. Results: No significant differences in allele, genotype, or haplotype frequencies of these two SNPs were noted among the three groups (P>0.05, respectively). Moreover, subjects with the NK2R 7853GG genotype had higher serum VEGF levels than those with GA or AA among the TDI-exposed workers (P=0.040). Conclusion: The NK2R 7853GG genotype may contribute to increased serum VEGF levels, which result in airway inflammation after TDI exposure.