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Background Asthma is a common respiratory disease that is characterized by bronchial hyperresponsiveness and airway obstruction due to chronic airway inflammation. Atopic asthma is a typical IgE-mediated disease in which the enhanced production of IgE is driven by the activation of Th2 cells, which release a distinct pattern of cytokines, including interleukin 4 (IL4) and IL3, in response to specific antigen presentation. To evaluate the methylation status of the whole genomes of bronchial mucosa tissues from subjects who lacked or had sensitization to Dermatophagoides farina (Df) and Dermatophagoides pteronyssinus (Dp). Methods The genome-wide DNA methylation levels in the bronchial mucosa tissues of atopic asthmatics (N = 10), non-atopic asthmatics (N = 7), and normal controls (N = 7) were examined using microarrays. Results In the bronchial mucosa of atopic asthmatics, hypermethylation was detected at 6 loci in 6 genes, while hypomethylation was detected at 49 loci in 48 genes compared to those of non-atopic asthmatics. Genes that were assigned the ontologies of multicellular organismal process, response to organic substance, hormone metabolic process, and growth factor receptor binding were hypomethylated. The methylation levels in the mucosa of asthmatics and normal controls were similar. Conclusions The bronchial mucosa of asthmatics who are atopic to Df or Dp have characteristic methylation patterns for 52 genes. The genes and pathways identified in the present study may be associated with the presence of atopy in asthmatics and therefore represent attractive targets for future research.

BackgroundWe previously demonstrated that single nucleotide polymorphism (SNP) and haplotypes were associated with aspirin hypersensitivity in asthmatics. We investigated the genetic effects of the SNPs and haplotypes on the expression of theCysLTR2gene.MethodsWe measured CysLTR2 protein and mRNA expression in EB virus-infected B cell lines from asthmatics havinght1+/+andht2+/+. A gel retardation assay was used to identify nuclear protein binding to the c.-819 promoter site. The function of promoter and 3'-UTR were assessed using pGL3 luciferase and pEGFP reporter system, respectively.ResultsWe found that the expression of CysLTR2 protein was higher in B cell lines of asthmatics havinght2+/+than in those havinght1+/+. PMA/ionomycin induced higher mRNA expression of CysLTR2 in B cell lines fromht2+/+asthmatics than those fromht1+/+asthmatics. A nuclear protein from the B cell lines showed stronger DNA binding affinity with a probe containingc.-819T thanone containingc.-819G. The luciferase activity of thec.-819Ttype ofCysLTR2promoter was higher than that of thec.-819Gtype. EGFP expression was higher in the EGFP-c.2078T3'-UTR fusion construct than in thec.2078Cconstruct.ConclusionThe sequence variants ofCysLTR2may affect its transcription and the stability of its mRNA, resulting in altered expression of CysLTR2 protein, which in turn causes some asthmatics to be susceptible to aspirin hypersensitivity.

Background Aspirin-intolerant asthma (AIA) occurs in the lower and upper airways through excessive production of leukotrienes upon administration of non-steroidal anti-inflammatory drugs (NSAIDs). One of the three symptoms of AIA is nasal polyposis, a chronic inflammatory disease that is related to the function of calcium ion in recruitment of immune cells during airway inflammation. It has been implicated that bronchodilation in the airway is related to Ca(2+) regulation. The calcium channel, voltage-dependent, gamma subunit 6 (CACNG6) gene encodes a protein that stabilizes the calcium channel. Methods To study the associations between AIA and polymorphisms in CACNG6 gene, eight variants were genotyped in 102 AIA cases and 429 aspirin-tolerant asthma (ATA) controls. Logistic analyses were used to evaluate the associations of CACNG6 polymorphisms with AIA. Results Statistical analyses revealed that a single nucleotide polymorphism (SNP; rs192808C > T; P = 0.0004, P corr = 0.0029, OR = 2.88 in co-dominant model; P = 0.0005, P corr = 0.0036, OR = 2.99 in dominant model) in intron and a haplotype unique to this variant (CACNG6_BL1_ht6; P = 0.003, P corr = 0.02, OR = 2.57 in co-dominant model, P = 0.001, P corr = 0.0087, OR = 2.81 in dominant model) were significantly associated with the risk of AIA. Conclusions Our results suggest that the CACNG6 variants might be associated with the risk of AIA in a Korean population.