RESUMEN
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.
Asunto(s)
Aspirina/efectos adversos , Asma Inducida por Aspirina/genética , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Predisposición Genética a la Enfermedad , Proteínas HSP70 de Choque Térmico/genética , Polimorfismo de Nucleótido Simple , Asma Inducida por Aspirina/etiología , Femenino , Humanos , Japón , Masculino , Persona de Mediana EdadRESUMEN
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.
Asunto(s)
Aspirina , Polimorfismo de Nucleótido Simple , Receptores de Formil Péptido/genética , Receptores de Tromboxano A2 y Prostaglandina H2/genética , Enfermedades Respiratorias/inducido químicamente , Enfermedades Respiratorias/genética , Células Th2/metabolismo , Adulto , Anciano , Alelos , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Células Th2/inmunologíaRESUMEN
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.
Asunto(s)
Asma Inducida por Aspirina/genética , Asma Inducida por Aspirina/inmunología , Interleucina-13/genética , Interleucina-13/inmunología , Interleucina-17/genética , Interleucina-17/inmunología , ADN/química , ADN/genética , Eosinofilia/sangre , Volumen Espiratorio Forzado/inmunología , Variación Genética , Genotipo , Humanos , Inmunoglobulina E/sangre , Japón , Modelos Logísticos , Persona de Mediana Edad , Análisis Multivariante , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: There has been no report that investigated ß(2)-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.
Asunto(s)
Asma Inducida por Aspirina/genética , Polimorfismo de Nucleótido Simple , Receptores Adrenérgicos beta 2/genética , Adulto , Anciano , Alelos , Sustitución de Aminoácidos , Arginina/genética , Pueblo Asiatico/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Glicina/genética , Humanos , Japón , Masculino , Persona de Mediana EdadAsunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Hidrocarburo de Aril Hidroxilasas/genética , Pueblo Asiatico/genética , Aspirina/efectos adversos , Asma Inducida por Aspirina/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo Genético , Antiinflamatorios no Esteroideos/inmunología , Aspirina/inmunología , Citocromo P-450 CYP2C19 , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: It has been reported that measurements of eosinophil-derived neurotoxin (EDN) may be useful for identifying eosinophil activities in allergic diseases including atopic dermatitis. METHODS: EDN concentrations in the urine were measured by enzyme-linked immunosorbent assay, and the number of eosinophils in the peripheral blood was counted in 30 patients with atopic dermatitis. The severity of atopic dermatitis was graded on the criteria proposed by Rajka and Langeland. The disease activity was assessed by each patient on a visual analogue scale (VAS). RESULTS: Urinary concentrations of EDN in patients with atopic dermatitis showed a significant positive correlation with disease severity. Urine EDN concentrations also correlated with VAS scores for itching, skin condition, overall skin symptoms and total VAS score, but not with the VAS score for skin dryness. Urinary EDN concentrations did not correlate with the number of eosinophils in the peripheral blood. CONCLUSIONS: The urinary EDN concentration in patients with atopic dermatitis is a useful clinical marker for monitoring disease activity.
