SummaryBackground and objective The thromboxane A2 receptor (TBXA2R) is a receptor for a potent bronchoconstrictor, TBXA2 which is known to be related to bronchial asthma and myocardial infarction. TBXA2R antagonist and TBX synthase inhibitors have been found to be effective in the management of asthmatic patients. This study was aimed to evaluate whether genetic variants of TBXA2R may be related with development of acetyl salicylic acid (ASA)-intolerant asthma (AIA). Methods TBXA2R gene polymorphisms (TBXA2R1795T4C, TBXA2R1924T4C) were determined using a single-base extension method in 93 AIA patients compared with 172 patients with ASA-tolerant asthma (ATA) and 118 normal controls (NCs) recruited from the Korean population. HLA DPB1*0301 genotype was performed using a direct sequencing method.Results The rare C allele frequency of TBXA2R1795T4C was significantly higher in AIA than in ATA (P 5 0.03) and the TBXA2R1795T4C polymorphism was also associated with extent of percent fall in forced expiratory volume in 1 s (FEV 1 ) after the inhalation of lysine-acetyl salicylic acid in AIA patients (P 5 0.009); AIA patients homozygous for the 1795 C allele had a greater percent fall of FEV 1 compared with individuals with TBXA2R1795 CT or TT genotypes. The frequency of patients carrying both the TBXA2R1795T4C rare allele and HLA DPB1*0301 was significantly higher in AIA patients (29.4%) than in ATA patients (7.3%) (P 5 0.008, odds ratio 5 5.3). Conclusion These results suggest that the polymorphism of TBXA2R1795T4C may increase bronchoconstrictive response to ASA, which could contribute to the development of the AIA phenotype.

SummaryBackground 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 4 A (Gly231Glu) and 11 424G 4 A (Arg375His), were genotyped using a single base extension method. The levels of PC 20 methacholine, specific IgE and IgG to TDI-human serum albumin conjugate, and serum vascular endothelial growth factor (VEGF), matrix metalloproteinase-9, and TGF-b1 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 4 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.