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-beta1 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).


CONCLUSIONS
The NK2R 7853GG genotype may contribute to increased serum VEGF levels, which result in airway inflammation after TDI exposure.
Ye
Y-M
YM
Department of Allergy & Rheumatology, Ajou University School of Medicine, Suwon, Korea.
Kang
Y-M
YM
Kim
S-H
SH
Kim
C-W
CW
Kim
H-R
HR
Hong
C-S
CS
Park
C-S
CS
Kim
H-M
HM
Nahm
D-H
DH
Park
H-S
HS
D000328:Adult; D001249:Asthma / Q000097:blood / Q000139:chemically induced / Q000235:genetics*; D005260:Female; D005541:Forced Expiratory Volume; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000097:blood / Q000139:chemically induced / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018041:Receptors, Neurokinin-2 / Q000235:genetics*; D014051:Toluene 2,4-Diisocyanate / Q000633:toxicity*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D018041:Receptors, Neurokinin-2; D042461:Vascular Endothelial Growth Factor A; D014051:Toluene 2,4-Diisocyanate; D007073:Immunoglobulin E