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장헌수,박종숙,장안수,박성우,우수택,김영훈,박춘식 대한천식알레르기학회 2011 Allergy, Asthma & Immunology Research Vol.3 No.4
Purpose: Aspirin-exacerbated respiratory disease (AERD) has attracted a great deal of attention because of its association with increased asthma severity. However, oral aspirin challenge (OAC) to diagnose AERD is a time-consuming procedure, and some patients experience serious complications. Thus, we evaluated diagnostic values of non-invasive clinical parameters to predict AERD in asthmatic patients. Methods: A total of 836 Korean subjects were recruited from an asthma cohort. They underwent OAC, and clinical parameters including the history of aspirin hypersensitivity,nasal polyposis, and chronic sinusitis of aspirin-tolerant asthma (ATA) and AERD asthmatic patients were compared. Results: Significant differences (P<0.01) were found in eight parameters: age at diagnosis, body mass index, FEV1%, PC20, history of urticaria, nasal polyps, chronic sinusitis,and history of aspirin hypersensitivity. After logistic regression analysis based on the eight clinical parameters, nasal polyps, history of aspirin intolerance, sinusitis, and log [PC20 methacholine] remained significantly associated with AERD (P<0.05). The sensitivity and specificity of the history of aspirin hypersensitivity to predict AERD were 64.7% and 92.0%, respectively, and the positive and negative predictive values were 56.9% and 94.1%, respectively. Overall, the accuracy of the test was 88.2%. The accuracy of the tests for nasal polyps and chronic sinusitis were 67.3% and 60.4%, respectively. Conclusions: Among clinical parameters associated with AERD, the history of aspirin hypersensitivity has the best positive and negative predictive values for the oral aspirin challenge test. Because the false-positive and -negative rates were still high, additional non-invasive methods are needed to reduce the rate of false outcomes.
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Asthma-Predictive Genetic Markers in Gene Expression Profiling of Peripheral Blood Mononuclear Cells
신승우,오태정,박세민,박종숙,장안수,박성우,우수택,안성환,박춘식 대한천식알레르기학회 2011 Allergy, Asthma & Immunology Research Vol.3 No.4
Purpose: We sought to identify asthma-related genes and to examine the potential of these genes to predict asthma, based on expression levels. Methods: The subjects were 42 asthmatics and 10 normal healthy controls. PBMC RNA was subjected to microarray analysis using a 35K array;t-tests were used to identify genes that were expressed differentially between the two groups. A multiple logistic regression analysis was applied to the differentially expressed genes, and area under the curve (AUC) values from receiver operating characteristic (ROC) curves were obtained.Results: In total, 170 genes were selected using the following criteria: P≤0.001 and ≥2-fold change. Among these genes, 57 were up-regulated and 113 were down-regulated in asthmatics versus normal controls. A multiple logistic regression analysis was done using more stringent criteria (P≤0.001 and ≥5-fold change), and eight genes were selected as candidate asthma biomarkers. Using these genes, 255 models (28-1) were generated. Among them, only 85 showed P≤0.05 by multiple logistic regression analysis. Based on the AUCs from ROC curves for the 85 models, we found that the best model consisted of the genes MEPE, MLSTD1, and TRIM37. The model showed 0.9928 of the AUC with 98% sensitivity and 80% specificity. Conclusions: MEPE, MLSTD1, and TRIM37 may be useful biomarkers for asthma.
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Putative association of RUNX1 polymorphisms with IgE levels in a Korean population
채수천,박병래,박춘식,류하정,양윤식,이수옥,최유현,김은미,우수택,김용훈,김가경,오범석,정헌택,김규찬,신형두 생화학분자생물학회 2006 Experimental and molecular medicine Vol.38 No.5
RUNX1, a member of the runt domain gene family of transcription factors, encodes a heterodimeric transcription factor and regulates the expression of hematopoiesis and myeloid differentiation. RUNX1 has been one of the target genes for research into various autoimmune disea-ses due to its properties as a transcription factor and functional distribution for chromosomal trans-location. In an effort to identify additional gene polymorphisms in which variants have been implicated in asthma, we investigated the genetic polymorphisms in RUNX1 to evaluate it as a potential candidate gene for a host genetic study of asthma and IgE production. We identified 19 sequence variants by direct DNA sequencing in 24 individuals of which four common variants were selected for genotyping in our asthma cohort (1,055 asthmatic patients, 384 normal controls). Using logistic regression analysis for association with the risk of asthma, while controlling for age, gender, and smoking status as of asthma were detected. However, two poly-morphisms in the promoter region (-2084G> C and -1282G>A) showed a marginal association with total IgE levels (0.03 and 0.03 in recessive models, respectively). Our findings suggest that poly-morphisms in RUNX1 might be one of the genetic factors for the regulation of IgE production
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