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

Abstract

Abstract.It is well known that aspirin-exacerbated respiratory disease (AERD) is more common in women than in men, however, whether gene polymorphisms of the thromboxane A 2 receptor (TBXA2R) and chemoattractant receptorhomologous molecules expressed on Th2 cells (CRTH2) are associated with the susceptibility of AERD remains unknown. In this study, we examined the gene polymorphisms in a Japanese population. DNA specimens were obtained from the following three groups: 96 patients with AERD, 500 patients with aspirin-tolerant asthma (ATA) and 100 normal controls. The target DNA sequence of each gene was amplified, and an allelic discrimination assay for single nucleotide polymorphisms relating to expression of each gene was carried out. The frequencies of the CC/CT genotype of TBXA2R +795T>C were higher than those of the TT genotype in AERD patients compared to ATA patients (P=0.015). In female AERD patients, but not in males, frequencies of the CC/CT genotype were higher than those of the TT genotype of TBXA2R +795T>C compared to female ATA patients (P=0.013). Also, frequencies of the TT genotype of CRTH2 -466T>C were higher than those of the CC/CT genotype in AERD patients compared to ATA patients (P=0.034). In female AERD patients, but not in male, frequencies of the TT genotype were higher than those of the CC/CT genotype of CRTH2 -466T>C in AERD patients compared to female ATA patients (P=0.046). Based on our investigations, no significant relationship was found between the genotype and the clinical characteristics according to these gene polymorphisms in AERD patients. Our results suggest that an association between the TBXA2R and CRTH2 gene polymorphisms with AERD may exist in the Japanese population.

Prostaglandins and Their Receptors in Eosinophil Function and As Therapeutic Targets

“…A single nucleotide polymorphism in the DP2 gene crth2 was also observed to correlate with increased levels of the eosinophil chemoattractant, eotaxin-2 in Korean AERD patients (171). Similarly, the prevalence of a crth2 single nucleotide polymorphism was found to be increased in a female Japanese AERD patient cohort (172). These findings suggest that targeting PGE 2 and PGD 2 receptors might provide potential novel treatment options for AERD.…”

Pharmacogenomics of Prostaglandin and Leukotriene Receptors

“…In patients with NERD the CRTH2 −466T>C polymorphism increases both serum and cellular eotaxin-2 production, and may lead to eosinophilic infiltration in these patients (Palikhe et al, 2010 ). Another study also showed that the frequency of the homozygous genotype for the less frequent allele of CRTH2 −466T>C was higher in NERD patients compared to aspirin-tolerant asthmatics (Kohyama et al, 2012 ). Interestingly, homozygous TT chronic urticaria patients required higher doses of antihistamines (Palikhe et al, 2009 ).…”

“…The frequencies of the CC/CT genotype of TBXA2R 795T>C were higher than those of the TT genotype in NERD patients compared to ASA-tolerant asthmatics (Kohyama et al, 2012 ). TBXA2R −4684C>T and 795T>C variants have also been associated with NERD (Kim et al, 2007b ).…”

Pharmacogenomics as a Tool for Management of Drug Hypersensitivity Reactions

“…SNPs in CYSLTR2 affecting gene expression have been associated with NERD [119]. The minor allele of the 795T9C TBXA2R polymorphism was found to be higher in NERD than in ASA-tolerant asthmatics [120], and the TBXA2R variant -4684T9C was associated with NIUA [121].…”