Bo-Young Cho

Combined effect of IL-10 and TGF-β1 promoter polymorphisms as a risk factor for aspirin-intolerant asthma and rhinosinusitis.

Background:  It has been known that interleukin (IL)‐10 promoter polymorphisms at −1082A/G, −819T/C and −592A/C, may influence IL‐10 expression and associate with asthma. Interleukin‐10 facilitates the regulatory function of transforming growth factor (TGF)‐β. The goal of this study was to investigate a gene–gene interaction between IL‐10 and TGF‐β1 polymorphisms in Korean asthmatics with aspirin hypersensitivity.

Association of three sets of high-affinity IgE receptor (FcepsilonR1) polymorphisms with aspirin-intolerant asthma

BACKGROUND AND OBJECTIVE The high-affinity IgE receptor comprises a tetramer of the ligand-binding alpha chain, a signal-augmenting beta chain, and a signal-transducing gamma chain dimer on mast cells. We hypothesized that the three subsets of the FCER1 gene may play a role in the development of the aspirin-intolerant asthma (AIA) phenotype and analyzed these genetic polymorphisms in association with clinical parameters in AIA patients. SUBJECTS AND METHODS Six polymorphisms of FCER1 (FCERIA-344C>T, FCER1A-95T>C, MS4A2-109T>C, MS4A2 E237G, FCER1G-237A>G, FCER1G-54G>T) were genotyped in 126 AIA patients compared to 177 patients with aspirin-tolerant asthma (ATA) and 222 normal health controls (NC). RESULTS A significant difference in the genotype frequencies of FCER1G-237A>G was detected between AIA and ATA patients (p<0.05) both in co-dominant and recessive analysis models, whereas no significant relationships were identified between the frequencies of the other five single-nucleotide polymorphisms and AIA, ATA, and NC subjects. In addition, AIA patients carrying the homozygous AA genotype of FCER1G-237A>G exhibited significantly higher total serum IgE levels than did those with the GG/AG genotype (p=0.012). AIA patients expressing the CT/TT genotype at FCERIA-344C>T showed a higher prevalence of serum IgE specific to Staphylococcal enterotoxin A than did those with the CC genotype (p=0.008). CONCLUSION The FCER1G-237A>G and FCERIA-344C>T polymorphisms may contribute to the development of AIA in a Korean population.

IL-13 Gene Polymorphisms are Associated With Rhinosinusitis and Eosinophilic Inflammation in Aspirin Intolerant Asthma

Purpose Aspirin-intolerant asthma (AIA) is characterized by moderate to severe asthma that is aggravated by aspirin or other non-steroidal anti-inflammatory drugs. Affected patients frequently have chronic rhinosinusitis and nasal polyposis due to persistent upper and lower airway inflammation with marked eosinophilia. IL-13 plays a crucial role in the development of allergic asthma by inducing airway eosinophilia and hyper-reactivity and it has been correlated with an increased eosinophil count. Methods Two promoter polymorphisms of the IL-13 gene (-1510 A>C and -1055C>T) and one coding nonsynonymus Arg110Gln (110G>A) polymorphism were genotyped using primer extension methods in 162 patients with AIA, 301 patients with aspirin-tolerant asthma (ATA), and 430 normal healthy controls (NC). Results There was no significant difference in the genotype, allele, and haplotype frequencies of the three polymorphisms among the three groups. AIA patients with the AA genotype -1510A>C (P=0.012) and CC genotype -1055C>T (P<0.001) had a significantly higher frequency of rhinosinusitis, as compared to those with the minor alleles of these two single nucleotide polymorphisms. AIA patients with the GG genotype had a higher peripheral eosinophil count (P=0.025) and a higher serum eotaxin-1 level (P=0.044), as compared to patients with the AA genotype IL-13 Arg110Gln (110G>A). Conclusions These findings suggest that the IL-13 polymorphisms at -1510A>C and 1055C>T are associated with the development of rhinosinusitis in AIA patients. IL-13 Arg110Gln may be associated with an increased eosinophil count and eotaxin-1 level and could increase eosinophilic inflammation in the upper and lower airways of patients with AIA.

Genetic variability in CRTH2 polymorphism increases eotaxin-2 levels in patients with aspirin exacerbated respiratory disease

To cite this article: Palikhe NS, Kim S‐H, Cho B‐Y, Ye Y‐M, Choi G‐S, Park H‐S. Genetic variability in CRTH2 polymorphism increases eotaxin‐2 levels in patients with aspirin exacerbated respiratory disease. Allergy 2010; 65: 338–346.

Histamine N-methyltransferase 939A>G polymorphism affects mRNA stability in patients with acetylsalicylic acid-intolerant chronic urticaria

Background:  Histamine plays an important role in allergic inflammation. Histamine levels are regulated by histamine N‐methyltransferase (HNMT).

Association of Four-locus Gene Interaction with Aspirin-intolerant Asthma in Korean Asthmatics

IntroductionAspirin-intolerant asthma (AIA), a major clinical presentation of aspirin hypersensitivity, affects 10% of adult asthmatics. The genetic risk factors involved in the susceptibility to AIA have recently been investigated, but multilocus single-nucleotide polymorphisms (SNPs) associated with this susceptibility has not been evaluated.MethodsWe examined 246 asthmatic patients: 94 having aspirin intolerance and 152 having aspirin tolerance. We selected 23 SNPs of 13 candidate genes and genotyped each SNP using a primer extension method. Multilocus genetic interactions were examined using multifactor dimensionality reduction (MDR) to test all multilocus SNP combinations to identify a useful SNP set for predicting the AIA phenotype.ResultsWe identified the best model using the MDR method, which consisted of a four-locus gene–gene interaction with 65.16% balanced accuracy and a cross-validation consistency of 70% in predicting AIA disease risk among asthmatic patients. This model included four SNPs such as B2ADR 46A>G, CCR3–520T>G, CysLTR1–634C>T, and FCER1B–109T>C.DiscussionThese results suggest that a multilocus SNP acts in combination to influence the susceptibility to aspirin intolerance in asthmatics and could be a useful genetic marker for the diagnosis of AIA.

Association of TNF-α promoter polymorphisms with aspirin-induced urticaria

Objective:  Although the pathogenesis of aspirin‐induced urticaria (AIU) is not fully understood, mast cell activation has been noted in patients with AIU. Tumour necrosis factor (TNF)‐α, a potent pro‐inflammatory cytokine, is released by human skin mast cells and other inflammatory cells in patients with urticaria. To investigate the role of TNF‐α promoter polymorphisms in the development of AIU, we performed an association study of TNF‐α promoter polymorphisms with AIU phenotype.

The SNP rs3128965 of HLA-DPB1 as a genetic marker of the AERD phenotype.

Background Two common clinical syndromes of acetylsalicylic acid (aspirin) hypersensitivity, aspirin-exacerbated respiratory disease (AERD) and aspirin-exacerbated cutaneous disease (AECD), were subjected to a genome-wide association study to identify strong genetic markers for aspirin hypersensitivity in a Korean population. Methods A comparison of SNP genotype frequencies on an Affymetrix Genome-Wide Human SNP array of 179 AERD patients and 1989 healthy normal control subjects (NC) revealed SNPs on chromosome 6 that were associated with AERD, but not AECD. To validate the association, we enrolled a second cohort comprising AERD (n = 264), NC (n = 238) and disease-control (aspirin tolerant asthma; ATA, n = 387) groups. Results The minor genotype frequency (AG or AA) of a particular SNP, rs3128965, in the HLA-DPB1 region was higher in the AERD group compared to the ATA or NC group (P = 0.001, P = 0.002, in a co-dominant analysis model, respectively). Comparison of rs3128965 alleles with the clinical features of asthmatics revealed that patients harboring the A allele had increased bronchial hyperresponsiveness to inhaled aspirin and methacholine, and higher 15-HETE levels, than those without the A allele (P = 0.039, 0.037, and 0.004, respectively). Conclusions This implies the potential of rs3128965 as a genetic marker for diagnosis and prediction of the AERD phenotype.