Association of thromboxane A2 receptor gene polymorphism with the phenotype of acetyl salicylic acid‐intolerant asthma

Abstract

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.

Thromboxane A2 receptor +795T>C and chemoattractant receptor-homologous molecule expressed on Th2 cells -466T>C gene polymorphisms in patients with aspirin-exacerbated respiratory disease

“…Genetic alteration of CRTH2 has been correlated to allergic asthma in African-American and Chinese populations (18), but not in a Japanese population (19). On the other hand, recent reports have shown a positive association of TBXA2R and CRTH2 polymorphisms with AERD susceptibility in a Korean population (20)(21)(22), and Akahoshi et al (26) showed that the -1933T>C SNP in the promoter region of TBX21 was associated with AERD in a Japanese population. However, to our knowledge, there has been no published data addressing the role of TBXA2R and CRTH2 gene polymorphisms in Japanese patients with AERD, and this is the first study to examine the relevance of genetic polymorphisms in these prostanoid receptors.…”

“…Two investigations from Korea demonstrated that the TBXA2R +795T>C gene polymorphism was associated with AERD susceptibility (20,21). Namely, the first report (20) showed that AERD patients had a significantly higher frequency of the combined homozygous CC genotype and heterozygous CT genotype group of TBXA2R +795T>C compared to ATA patients, and the second (21) showed that the frequency of CC homozygotes of TBXA2R +795T>C was higher in AERD patients than in ATA patients.…”

“…Namely, the first report (20) showed that AERD patients had a significantly higher frequency of the combined homozygous CC genotype and heterozygous CT genotype group of TBXA2R +795T>C compared to ATA patients, and the second (21) showed that the frequency of CC homozygotes of TBXA2R +795T>C was higher in AERD patients than in ATA patients. Furthermore, a recent investigation in a Korean population found that AERD patients exhibited a significantly higher frequency of the homozygous TT genotype of CRTH2 -466T>C compared to ATA patients (22), indicating that our findings may correspond to the results of the Korean study on the TBXA2R +795T>C and CRTH2 -466T>C gene polymorphism in AERD patients (20)(21)(22). However, neither of the reports from Korea showed the subgroup analyses with gender of the TBXA2R +795T>C and CRTH2 -466T>C gene polymorphism in the patients.…”

“…Investigations into the association between AERD susceptibility and prostanoid gene polymorphisms in a Korean population have shown that, among three single-nucleotide polymorphisms (SNPs) of the TBXA2R gene investigated, the +795T>C polymorphism was only associated with AERD susceptibility (20,21) and the -466T>C polymorphism of the CRTH2 gene was associated with AERD (22). However, there has been no published data addressing the role of TBXA2R and CRTH2 gene polymorphisms in Japanese patients with AERD.…”

Association of polymorphisms in thromboxane A2 receptor and thromboxane A synthase 1 with cerebral infarction in a Korean population

“…The TaqMan assay was performed as described previously (30,31). One allelic probe was labeled with the FAM dye and the other with the fluorescent VIC dye.…”