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Background: There has been no report that investigated β₂-adrenergic receptor (ADRB2) gene polymorphism in patients with aspirin-exacerbated respiratory disease (AERD). Methods: DNA in the specimens in three groups of study subjects classified patients with AERD, patients with aspirin-tolerant asthma (ATA) and normal controls was extracted, and the target DNA sequence of the ADRB2 was amplified using a set of primers to generate an amplicon of 219 bp in length. Allelic discrimination assay for single nucleotide polymorphisms relating to the ADRB2 gene expression was carried out by using a previously described single nucleotide polymorphism detective system, sequence-specific thermal-elution chromatography. Results: The frequency of the Gly variant allele in patients with AERD was significantly lower than that in patients with ATA (p = 0.007), and the odds ratio (OR) of AERD to ATA associated with wild-type ArgArg homozygote was 3.300. Frequencies of wild-type ArgArg homozygote are significantly higher than those of variant-type ArgGly/GlyGly genotype in patients with AERD compared with those with ATA (p < 0.001, OR = 3.153). In patients with AERD, frequencies of wild-type ArgArg homozygote in both female and male patients are significantly higher than those of variant-type ArgGly/GlyGly genotype in male patients compared with those with ATA (p < 0.001, OR = 5.128 and p = 0.007, OR = 4.367, respectively). Also, in patients with AERD, frequencies of wild-type ArgArg homozygote in female patients are significantly higher than those of variant-type ArgGly/GlyGly genotype in female patients compared with those with ATA (p = 0.002, OR = 2.825). Conclusions: We were the first to analyze Arg16Gly ADRB2 gene polymorphism in Japanese patients with AERD, and showed that Arg16Gly ADRB2 gene polymorphism in Japanese patients with AERD is different from that in the patients with ATA.

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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.

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Background and Aims: The mortality rate from disseminated intra-

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