Shyuzo Abe

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.

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 A2 receptor (TBXA2R) and chemoattractant receptor-homologous 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.

Arg16Gly β2-Adrenergic Receptor Gene Polymorphism in Japanese Patients with Aspirin-Exacerbated Respiratory Disease

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.

IL-13 and IL-17A gene polymorphisms in Japanese patients with aspirin-exacerbated respiratory disease

BACKGROUND The role of interleukin (IL) 13 and IL-17A in aspirin-exacerbated respiratory disease (AERD) remains unknown. OBJECTIVE To analyze the IL-13 and IL-17A gene polymorphisms in Japanese patients with AERD. METHODS The single-nucleotide polymorphisms in each gene were examined in patients with AERD, patients with aspirin-tolerant asthma (ATA), and healthy controls. RESULTS Frequencies of the TT/CT genotype of the IL-13 -1111C>T gene were higher than frequencies of the CC genotype in AERD patients compared with ATA patients (P < .001). In female patients with AERD, frequencies of the TT/CT genotype were higher than those of the CC genotype compared with female patients with ATA (P < .001). However, genotype frequencies of IL-13 Arg110Gln did not differ between AERD and ATA patients. Frequencies of the CC genotype of the IL-17A -737C>T gene were higher than those of the TT/CT genotype in AERD patients compared with ATA patients (P = .02). In female patients with AERD, frequencies of the CC genotype were higher than those of the TT/CT genotype compared with female patients with ATA (P = .03). Forced expiratory volume in 1 second (percentage predicted) in AERD patients with the CC genotype of the IL-13 -1111C>T gene was lower than that in the patients with the TT/CT genotype. AERD patients with the TT/CT genotype of the IL-17A -737C>T gene had a higher peripheral total eosinophil count compared with the patients with the CC genotype. The comparison of the clinical characteristics according to the IL-13 Arg110Gln gene polymorphism showed no difference. CONCLUSIONS These findings suggest that the IL-13 -1111C>T and IL-17A -737C>T gene sequence variations might have a role in the development of AERD.

Heat shock protein 70 gene polymorphisms in Japanese patients with aspirin-exacerbated respiratory disease.

Background Aspirin-exacerbated respiratory disease (AERD) is nonatopic asthma, and the role of heat shock protein (HSP) 70 in AERD remains unknown. We analyzed HSP70 gene polymorphisms in Japanese patients with AERD. Methods The single-nucleotide polymorphisms in HSPA1B-179C>T and 1267A>G gene were examined in patients with AERD and those with aspirin-tolerant asthma (ATA). All patients were in a stable condition. Results There were significant differences in total serum IgE levels, peripheral blood eosinophil count, and prevalence of atopy between AERD and ATA. The patients with AERD showed higher frequencies of the CT/TT genotype of the HSPA1B-179C>T than that of the CC genotype compared to ATA (P < 0.001). They showed higher frequencies of the GG genotype of the HSPA1B1267A>G than that of the GA/AA genotype compared to ATA (P < 0.001). These differences were irrespective of the sex for the genotypes analyzed. The frequency of HSPA1B-179C/1267A haplotype was significantly higher in AERD compared to ATA (P < 0.001; odds ratio, 3.154; 95% confidence interval, 1.916-5.193). Among the clinical and hematological characteristics investigated, AERD showed a significant variance in peripheral blood eosinophil count according to the association of the 2 HSP70 gene polymorphisms (P = 0.033), but not in ATA. Conclusions Our findings first suggest that the association between HSPA1B-179C>T and 1267A>G gene sequence variations might be implicated in the development of AERD.