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

• Published in: Clinical and experimental allergy Vol. 36; no. 9; pp. 1153 - 1160
• Main Authors: Ye, Y.-M., Kang, Y.-M., Kim, S.-H., Kim, C.-W., Kim, H.-R., Hong, C.-S., Park, C.-S., Kim, H.-M., Nahm, D.-H., Park, H.-S.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2006; Blackwell
• Subjects: Adult; Allergic diseases; asthma; Asthma - blood; Asthma - chemically induced; Asthma - genetics; Biological and medical sciences; Female; Forced Expiratory Volume; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Frequency - genetics; Genetic Predisposition to Disease - genetics; genetic susceptibility; Genotype; Haplotypes - genetics; Humans; Immunoglobulin E - blood; Immunopathology; isocyanate; Male; Medical sciences; Middle Aged; neurokinin 2 receptor; Occupational Diseases - blood; Occupational Diseases - chemically induced; Occupational Diseases - genetics; Polymorphism, Single Nucleotide - genetics; Receptors, Neurokinin-2 - genetics; Toluene 2,4-Diisocyanate - toxicity; Vascular Endothelial Growth Factor A - blood; Human; Isocyanates; neurokinin 2 receptor; Immunopathology; Lung disease; Allergy; Genetic variability; Respiratory disease; isocyanate; Genotype; Asthma; Immunology; Vascular endothelium growth factor; Bronchus disease; Genetics; Serum; Obstructive pulmonary disease; genetic susceptibility; Biological receptor
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2006.02547.x

Summary 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.