Jungseob Lee

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.

Fast detection of high-order epistatic interactions in genome-wide association studies using information theoretic measure

There are many algorithms for detecting epistatic interactions in GWAS. However, most of these algorithms are applicable only for detecting two-locus interactions. Some algorithms are designed to detect only two-locus interactions from the beginning. Others do not have limits to the order of interactions, but in practice take very long time to detect higher order interactions in real data of GWAS. Even the better ones take days to detect higher order interactions in WTCCC data. We propose a fast algorithm for detection of high order epistatic interactions in GWAS. It runs k-means clustering algorithm on the set of all SNPs. Then candidates are selected from each cluster. These candidates are examined to find the causative SNPs of k-locus interactions. We use mutual information from information theory as the measure of association between genotypes and phenotypes. We tested the power and speed of our method on extensive sets of simulated data. The results show that our method has more or equal power, and runs much faster than previously reported methods. We also applied our algorithm on each of seven diseases in WTCCC data to analyze up to 5-locus interactions. It takes only a few hours to analyze 5-locus interactions in one dataset. From the results we make some interesting and meaningful observations on each disease in WTCCC data. In this study, a simple yet powerful two-step approach is proposed for fast detection of high order epistatic interaction. Our algorithm makes it possible to detect high order epistatic interactions in GWAS in a matter of hours on a PC.

A case of occupational asthma and rhinitis caused by Sanyak and Korean ginseng dusts.

Sanyak has been used as a food and herbal material for various symptoms in oriental medicine. There have been few reports of occupational asthma induced by herb materials (1–6). Until now there has been no account of occupational asthma caused by Korean ginseng. We describe a case of occupational asthma and rhinitis caused by Sanyak (Dioscorea batatas) and Korean ginseng (Panax ginseng), as confirmed by specific inhalation challenge tests. A 29-year-old female patient was presented to the emergency department (ED) of Eulji University Hospital in Daejeon, Korea, for the treatment of dyspnea, wheezing, and cough. The patient had been incidentally exposed to airborne Sanyak dust, during the process of grinding dried Sanyak into powder, 5 min before the onset of symptoms. She had been a merchant of herbal materials for the previous 26 months. Twelve months before her visit, she had been admitted to another hospital and diagnosed with bronchial asthma after the sudden onset of dyspnea following an exposure to airborne ginseng dust. The patient had been suffering from nasal itching, sneezing, rhinorrhea, and nasal obstruction during the spring season for 6 years and had also experienced itching and swelling of the lips, tongue, and throat after ingesting fresh chestnut, sweet potato, and ginseng. The patient was a non-smoker and had no family history of allergic diseases. The patient appeared acutely ill and had tachypnea. Diffuse expiratory wheezes were noted over both lung fields. Arterial blood gas measurements at the ED indicated a pH of 7.414, PaCO2 of 30.8 mmHg, PaO2 of 70.4 mmHg and SaO2 94.6%. The total IgE level was 663.0 IU/ml. After pharmacological treatment, her symptoms resolved in a day. Proteins were extracted from Ginseng and Sanyak, and used for skin-prick tests, inhalation challenge tests, and laboratory studies. The skin-prick testing was expressed as mean wheal diameter/ mean erythema diameter (in millimeters): Dermatophagoides pteronyssinus 6.5/23.5 (Allergopharma, Reinbek, Germany); alder tree pollen 5.5/33.5 (Allergopharma); birch tree pollen 3.5/17 (Allergopharma); ginseng (1 : 100 w/v) 3/12; Sanyak (1 : 100 w/v) 3.75/19; histamine 4/17.5; and saline 0/0. Nonspecific and specific challenge tests were performed during her stable state. The methacholine bronchial challenge test revealed a 20% decline of forced expiratory volume in 1 s[FEV1] at the concentration of 0.75 mg/ml. The bronchoprovocation tests showed early asthmatic responses to both Sanyak and ginseng extracts (1 : 1000 and 1 : 100 w/ v, respectively). Serum-specific IgE and IgG4 antibodies to Sanyak were detected by enzyme linked immunosorbent assay[ELISA], but there was no specific antibody binding to ginseng. The sodium dodecyl sulphate-polyacrylamide gel electrophoresis[SDS-PAGE] and an IgEimmunoblot, a 35-kDa IgE-binding component was detected in the Sanyak extracts (Fig. 1), but no IgE-binding component was noted in the ginseng extract. The ELISA inhibition test, specific IgE binding, and IgG4 binding to Sanyak demonstrated specific, dosedependent inhibition by Sanyak extracts but not by other control agents. The patient in this study showed the occurrence of occupational asthma induced by Sanyak and Korean ginseng. Although there is a report of occupational asthma being induced by Brazilian ginseng (1) no cases of bronchial asthma caused by Korean ginseng have been previously reported. Brazilian ginseng and Korean ginseng are different plants in terms of taxonomic classification. Brazilian ginseng (Pfaffia paniculata) belongs to the Amaranthaceae family; in contrast, the Korean ginseng (Panax ginseng) belongs to the Araliaceae family (1). This study, it is suggested that Sanyakderived allergen can induce IgE-mediated allergic reactions. We were unable to demonstrate specific IgE and IgG4 antibodies to Korean ginseng extract despite the fact that the patient showed a positive bronchial provocation and positive responses to a skin-prick test. Further studies are needed to investigate the pathogenic mechanism of occupational asthma caused by Korean ginseng. This study was funded by the Korean government (A0505171).

Topological Entropy Dimension and Directional Entropy Dimension for ℤ2-Subshifts

The notion of topological entropy dimension for a Z -action has been introduced to measure the subexponential complexity of zero entropy systems. Given a Z 2 -action, along with a Z 2 -entropy dimension, we also consider a finer notion of directional entropy dimension arising from its subactions. The entropy dimension of a Z 2 -action and the directional entropy dimensions of its subactions satisfy certain inequalities. We present several constructions of strictly ergodic Z 2 -subshifts of positive entropy dimension with diverse properties of their subgroup actions. In particular, we show that there is a Z 2 -subshift of full dimension in which every direction has entropy 0.

Cluster Analysis of SNPs with Entropy Distance and Prediction of Asthma Type Using SVM

Single nucleotide polymorphisms (SNPs) are a very important tool for the study of human genome structure. Cluster analysis of the large amount of gene expression data is useful for identifying biologically relevant groups of genes and for generating networks of gene-gene interactions. In this paper we compared the clusters of SNPs within asthma group and normal control group obtained by using hierarchical cluster analysis method with entropy distance. It appears that the 5-cluster collections of the two groups are significantly different. We searched the best set of SNPs that are useful for diagnosing the two types of asthma using representative SNPs of the clusters of the asthma group. Here support vector machines are used to evaluate the prediction accuracy of the selected combinations. The best combination model turns out to be the five-locus SNPs including one on the gene ALOX12 and their accuracy in predicting aspirin tolerant asthma disease risk among asthmatic patients is 66.41%.