Association between Maternal Characteristics and Neonatal Birth Weight in a Korean Population Living in the Seoul Metropolitan Area, Korea: A Birth Cohort Study (COCOA)

신윤호,권지원,최석주,김경원,유진호,안강모,김형영,서주희,김효빈,심정연,김우경,권지원,이수영,장광천,권자영,이경주,박희진,이필량,원혜성,홍수종,송대진,김병주,이소연 대한의학회 2013 Journal of Korean medical science Vol.28 No.4

Previous studies suggest that maternal characteristics may be associated with neonatal outcomes. However, the influence of maternal characteristics on birth weight (BW) has not been adequately determined in Korean populations. We investigated associations between maternal characteristics and BW in a sample of 813 Korean women living in the Seoul metropolitan area, Korea recruited using data from the prospective hospital-based COhort for Childhood Origin of Asthma and allergic diseases (COCOA) between 2007 and 2011. The mean maternal age at delivery was 32.3 ± 3.5 yr and prepregnancy maternal body mass index (BMI) was 20.7 ± 2.5 kg/m2. The mean BW of infant was 3,196 ± 406 g. The overall prevalence of a maternal history of allergic disease was 32.9% and the overall prevalence of allergic symptoms was 65.1%. In multivariate regression models,prepregnancy maternal BMI and gestational age at delivery were positively and a maternal history of allergic disease and nulliparity were negatively associated with BW (all P < 0.05). Presence of allergic symptoms in the mother was not associated with BW. In conclusion,prepregnancy maternal BMI, gestational age at delivery, a maternal history of allergic disease, and nulliparity may be associated with BW, respectively.

DNA Hypermethylation of Tumor-Related Genes in Gastric Carcinoma

홍수형,김호각,정윤복,김은영,이종영,윤상모,권중구,손윤경,곽은경,김정완 대한의학회 2005 Journal of Korean medical science Vol.20 No.2

The hypermethylation of the CpG islands is a common mechanism for the inacti-vation of tumor-related genes. In the present study, we analyzed the methylation status of genes for cell repair such as hMLH1, MGMT, and GSTP1, and a gastric cancer-specifically methylated DNA fragment, MINT 25 in gastric cancer cases and control groups. The study population consisted of 100 gastric cancer patients (50 distal and 50 proximal carcinomas), and 238 healthy controls. All genes showed more frequent hypermethylation in the cases than in the control group (p<0.0001). We investigated the association between promoter hypermethylation and relevant parameters including age, gender, alcohol consumption, smoking, and family his-tory. There was a common hypermethylation of hMLH1 (p=0.008), MGMT (p= 0.0001), and GSTP1 (p=0.0003) in females. This study also demonstrates that hypermethylation was strongly associated with non-drinkers (MGMT, p=0.046 and MINT 25, p=0.049) and non-smokers (hMLH1, p=0.044; MGMT, p=0.0003; MINT 25, p=0.029). Moreover, the frequency of MINT 25 hypermethylation increased with age (p=0.037), and MGMT methylation was frequently detected in distal gas-tric cancer than in proximal type (p=0.038). Our study suggested that promoter hypermethylation of the genes involved in cell repair system and MINT 25 is asso-ciated strongly with some subgroups of primary gastric carcinoma.

새로운 천식 표현형의 등장

권지원,홍수종 대한 소아알레르기 호흡기학회 2012 Allergy Asthma & Respiratory Disease Vol.22 No.2

Asthma is a complex and heterogeneous disease, which is comprised of seperate phenotypes sharing common characteristics, such as airway inflammation, bronchial hyperresponsiveness and variable airflow limitation. Traditionally, asthma phenotypes have been described by combinations of clinical characteristics, according to the expert’s recommendation, but they are now focusing on the pathobiologic mechanisms often using exploratory statistical methods. Several phenotypes and endotypes have been suggested by biased or unbiased phenotyping approaches. However, more detailed studies are still needed. In the future, more integrated large-scaled consortium of cohorts,including clinical information, genetics, molecular biology, and experiments will promote to understand the pathobiologic mechanisms of asthma phenotypes for the personalized therapy.

Association Between Serum IgE Levels and the CTLA4 +49A/G and FCER1B -654C/T Polymorphisms in Korean Children With Asthma

홍수종,오규영,강미진,최원아,권지원,김병주,유진호 대한천식알레르기학회 2010 Allergy, Asthma & Immunology Research Vol.2 No.2

Purpose: T cells play a central role in cell-mediated immunity, atopic disease, and asthma. The balance of CD28/cytotoxic T-lymphocyte antigen 4(CTLA4)-derived signal transduction plays an important role in the activation of T cells and an increased immunoglobulin E (IgE) response. The aim of the current study was to investigate the association between polymorphisms in the genes encoding both CTLA4 and the high-affinity IgE receptor 1B (FCER1B) and serum IgE levels in Korean children with asthma. Methods: We enrolled 238 controls and 742 children with asthma. The CTLA4 +49A/G and FCER1B -654C/T polymorphisms were genotyped by PCR-restriction fragment length polymorphism analysis. Results: We observed no difference in the distribution of CTLA4 +49A/G among controls, children with asthma, and those with atopic asthma. In contrast, the GA genotype of CTLA4 +49A/G in children with atopic asthma was significantly higher compared to that in those with non-atopic asthma. Moreover, significantly higher log Dp/Df-specific IgE levels were found in children with asthma and those with atopic asthma carrying one or two copies of the CTLA4 +49A versus those homozygous for +49G. Gene-gene interactions between CTLA4 and FCER1B with the heterozygote and homozygote of variant genotypes were associated with the log Dp/Df-specific IgE levels, but not asthma development. In addition, children with Dp/Df (+)asthma carried an elevated combined genotype of risk allele compared to those with Dp/Df (-) asthma. Conclusions: The CTLA4 +49A/G polymorphism may contribute to the production of IgE in Korean children with asthma, especially in Dp/Df-specific IgE levels, but not in the direct development of asthma. In addition, Dp/Df-specific IgE levels with a FCER1B -654C/T polymorphism may involve additive effects.

The Effects of Lactobacillus rhamnosus on the Prevention of Asthma in a Murine Model

홍수종,유진호,장성옥,김병주,송영화,권지원,강미진,최원아,정현돈 대한천식알레르기학회 2010 Allergy, Asthma & Immunology Research Vol.2 No.3

Purpose: Lactobacilli are probiotic bacteria that are effective in the management of allergic diseases or gastroenteritis. It is hypothesized that such probiotics have immunoregulatory properties and promote mucosal tolerance. Our goal was to investigate whether Lactobacillus casei rhamnosus Lcr35 could inhibit airway inflammation in an ovalbumin (OVA)-induced murine model of asthma. Methods: BALB/c mice aged 6 weeks were used in the present study. Lactobacillus casei rhamnosus Lcr35 was administered daily, starting 1 week prior to the first OVA sensitization (group 1) and 2days before the first 1% OVA airway challenge (group 2). Mice that received only saline at both sensitization and airway challenge time points were used as negative controls (group 3), and those that had OVA-induced asthma were used as positive controls (group 4). Airway responsiveness to methacholine was assessed, and bronchoalveolar lavage (BAL) was performed. At the endpoint of the study, total IgE as well as OVA-specific IgE,IgG1 and IgG2a in serum was measured by enzyme-linked immunosorbent assay. Lung pathology was also evaluated. Results: Airway hyperresponsiveness,total cell counts and the proportion of eosinophils in BAL fluid were significantly decreased in group 1 compared with group 4 (P<0.05). Total serum IgE levels were also significantly decreased in group 1 compared with group 4. Serum levels of OVA-specific IgE, IgG1 and IgG2a were not significantly influenced by treatment with Lcr35. There was significantly less peribronchial and perivascular infiltration of inflammatory cells in group 1 compared with group 4; however, there were no significant differences in methacholine challenge, BAL, serology or histology between groups 2and 4. Conclusions: Oral treatment with Lcr35 prior to sensitization can attenuate airway inflammation and hyperreactivity in a mouse model of allergic airway inflammation. These results suggest that Lcr35 may have potential for preventing asthma.

Smoking-Induced Acute Eosinophilic Pneumonia in a 15-year-old Girl: A Case Report

홍수종,윤지석,권지원,김병주 대한천식알레르기학회 2010 Allergy, Asthma & Immunology Research Vol.2 No.2

Acute eosinophilic pneumonia is a very rare disease that is characterized by acute febrile respiratory failure, diffuse bilateral infiltrates on chest X-ray,and eosinophilia in bronchoalveolar lavage fluid in the absence of infection. We present the case of a 15-year-old girl diagnosed with smoking-induced acute eosinophilic pneumonia. A previously healthy young girl with a 1-day history of fever presented with cough, dyspnea, and diffuse bilateral infiltrates on chest X-ray. She had started smoking only 3 weeks before presentation. She was diagnosed by bronchoalveolar lavage fluid tests and lung biopsy and dramatically improved after steroid treatment. We emphasize that acute eosinophilic pneumonia must be considered when acute pneumonia does not respond to broad-spectrum antibiotics. Effective treatment and prompt institution of therapy can obviate unnecessary morbidity and mortality.

서울 송파지역 초등학생에서 알레르기비염 유병률과 항원 감작과의 관련성

권지원,홍수종,서주희,유진호,김병주,김효빈,이소연,김우경,김경원,지혜미,김규언,신의진,김명희,김호 대한 소아알레르기 호흡기학회 2011 Allergy Asthma & Respiratory Disease Vol.21 No.1

Purpose:We investigated the relationship between allergic rhinitis (AR) and allergen sensitization in students at an elementary school in Seoul. Methods:A modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire survey was administered to 1,376 elementary school children in the Songpa area of Seoul. Serum total IgE, blood eosinophils, and skin prick tests for 18 common allergens were performed. Results:The prevalence of AR symptoms during the last 12 months and the current AR, defined as having AR symptoms during last 12 months with a history of AR diagnosis from the doctor, were 39.0% and 24.2%, respectively. Males were more likely to have current AR than females (26.6% vs. 21.5%, P=0.04). Independent risk factors for current AR were parental allergic disease (adjusted odds ratio [aOR], 3.78, 95% CI, 2.76-5.18), history of atopic dermatitis (AD; aOR, 1.47; 95% CI, 1.05-2.04), history of asthma (aOR, 3.48; 95% CI, 2.15-5.61), and higher maternal education (aOR, 1.42; 95% CI, 1.02-1.99). The subjects with higher quartiles of serum total IgE (P value for trend <0.001), more than 4% of eosinophil fraction (aOR 1.76; 95% CI, 1.24-2.48), and allergen sensitization house dust mites [aOR, 1.54; 95% CI, 1.10-2.15], dog [aOR, 2.95; 95% CI, 1.38-6.28], cat [1.85; 95% CI, 1.02-3.34], Alternaria [aOR, 2.37; 95% CI, 1.06-5.32] and late- blooming tree pollen mixture [aOR 2.26; 95% CI, 1.12-4.57] were more likely to have current AR. Conclusion:The prevalence of AR in children has increased during the last decade. The sensitization to common allergens and increased sensitization were associated with the development of current AR. House dust mites, dog, cat, alder, and Alternaria were the important allergens for current AR. 목적:본 연구는 서울지역 초등학생 알레르기비염 유병률 및 위험인자를 확인하기 위해 시행되었다. 방법:연구대상은 서울 송파지역 1개 초등학교 학생 1,376명(남아 740명, 여아 636명)이었고, 개량된 ISAAC 설문지를 통해 알레르기비염의 유병률 분석을 시행하였고, 알레르기 피부반응검사 및 혈액 내 총 IgE, 호산구 분율 검사를 시행하여 생체지표에 따른 현증 알레르기비염의 위험도를 분석하였다. 결과:설문지의 회수율은 98.3%였고, 대상군의 연령은 9.43±1.76세였고 남아가 746명, 여아가 636명으로 남녀의 비율은 53.8%, 46.2%였다. 최근 12개월 내 알레르기비염 증상 유병률은 39.0%, 알레르기비결막염 증상 유병률은 13.1%였으며, 평생 동안 의사에게 진단받은 알레르기비염의 유병률은 38.5%, 최근 12개월 내에 알레르기비염 치료 유병률은 29.5% 였다. 현증 알레르기비염의 유병률은 24.2 %였다. 현증 알레르기비염의 위험인자로는 아토피피부염 진단 병력(aOR=1.47, 95% CI 1.05-2.04), 천식 진단 병력(aOR=3.48, 95% CI 2.15-5.61), 부모의 알레르기질환(aOR=3.78, 2.76-5.18), 어머니의 대졸이상 학력 (aOR=1.42, 95% CI 1.02-1.99) 등이 있었다. 또한 호산구 분율이 높을수록(P value for trend =0.001), 혈청 IgE가 높을수록(P value for trend <0.001), 알레르겐 감작수가 많을수록(P value for trend <0.001) 위험도가 증가하였다. 집먼지진드기(1.54, 1.10-2.15), 개 항원(2.95, 1.38-6.28), 고양이 항원(1.85, 1.02-3.34), 오리나무 (2.71, 1.09-6.71), Alternaria 감작(2.37, 1.06-5.32)은 현증 알레르기비염의 독립적인 위험인자였다. 결론:서울 초등학교 알레르기비염 유병률은 과거 자료와 비교하여 증가하고 있으며, 아토피피부염과 천식의 병력, 부모의 알레르기질환력, 모의 높은 교육수준 등의 경우에 그 위험도가 높았다. 혈액 내 호산구 분율, 혈청 IgE, 알레르겐 감작수는 현증알레르기비염과 용량반응관계의 위험도를 보였으며, 집먼지진드기, 개, 고양이 항원, 오리나무, Alternaria는 서울 송파지역 초등학생 알레르기비염의 주요 원인 항원이었다.

Changes in the Prevalence of Childhood Asthma in Seoul from 1995 to 2008 and Its Risk Factors

권지원,김병주,송영화,서주희,김태희,유진호,김효빈,이소연,김우경,김경원,지혜미,김규언,김호,홍수종 대한천식알레르기학회 2011 Allergy, Asthma & Immunology Research Vol.3 No.1

Purpose: To investigate the prevalence of asthma and determine its risk factors in elementary school students in Seoul. Methods: A modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used to survey 4,731 elementary school students from five areas in Seoul between April and October, 2008. Results: In elementary school children, the lifetime and recent 12-month prevalence of wheezing were 11.7% and 5.6%, respectively. The lifetime prevalence of asthma diagnosis was 7.9%, and the recent 12-month prevalence of asthma treatment was 2.7%. Male sex (adjusted odds ratio [aOR], 1.90; 95% confidence interval [CI], 1.36–2.66), history of atopic dermatitis (AD) (aOR, 2.76; 95% CI, 1.98–3.84), history of allergic rhinitis (AR) (aOR, 3.71; 95% CI, 2.61–5.26), history of bronchiolitis before 2 years of age (aOR, 2.06; 95% CI, 1.39–3.07), use of antibiotics during infancy for >3 days (aOR, 1.88; 95% CI, 1.35–2.62), parental history of asthma (aOR, 2.83; 95% CI, 1.52–5.27), exposure to household molds during infancy (aOR, 1.84; 95% CI, 1.18–2.89), and the development or aggravation of asthma symptoms within 6 months after moving to a new house (aOR, 11.76; 95% CI, 5.35–25.86) were the independent risk factors for wheezing within 12 months. Conclusions:The prevalence of wheezing and asthma in elementary school students in 2008 was similar to that in the past decade. Male sex, history of AD, history of AR, history of bronchiolitis before 2 years of age, parental asthma, use of antibiotics during infancy, exposure to molds in the house during infancy, and development or aggravation of asthma symptoms within 6 months after moving to a new house, could be risk factors for wheezing within 12 months.

미백과 항산화에 미치는 백복령, 감초, 유백피 추출 혼합물의 영향

권은정(Eun-Jeong Kwon),박혜정(Hye-Jung Park),남향(Hyang Nam),이수경(Su-Gyeng Lee),홍수경(Su-gyoung Hong),김문무(Moon-Moo Kim),이경록(Kyeong Rok Lee),홍일(Il Hong),이도경(Do Gyeong Lee),오영희(Yunghee Oh) 한국생명과학회 2014 생명과학회지 Vol.24 No.10

활성산소는 피부손상을 일으키는 지질, 단백질, DNA의 산화를 유발시킨다. 더욱이활성산소는 기미, 검버섯, 주근깨를 생성하는 멜라닌생성과정을 촉진시킨다. 수많은 생약재중에서, 백복령, 감초, 유백피는 각각 parchymic acid, glabridin 및 flavonoid 를 함유하고 있다고 보고되어 있다. 본 연구의 목적은 기능성 미백화장품을 개발하기 위하여 B16F1 세포에서 백복령, 감초, 유백피 혼합추출물(PGUE)의 항산화 및 미백효과를 조사하는 것이다. PGUE는 높은 환원력 뿐만 아니라 DPPH radical 및 지질과산화 억제효과를 나타내었다. 항산화효과 뿐만 아니라 PGUE는 양성대조군으로 사용된 arbutin과 비교하여 melanogenesis와 관련 있는 tyrosinase 효소활성을 크게 감소 시켰다. 더욱이 PGUE는 살아있는 melanome세포에서 melanin합성을 억제하였다. 또한 PGUE는 superoxide dismutase-1 (SOD-1)및 tyrosinase related protein-1 (TRP-1) 단백질 발현을 억제시킨다는 것이 발견되었다. 이러한 결과들은 PGUE가 피부에 대한 항산화효과 및 미백효과를 가지고 있다는 것을 나타내어, 기능성 미백화장품의 개발을 위한 유효한 성분으로 이용되어 질 수 있다는 것을 암시하고 있다. Reactive oxygen species (ROS) are known to lead to oxidation of lipids, proteins, and DNA and cause skin damage. Moreover, ROS promote melanogenesis, which causes melasma, age spots, and freckle. The main compounds of the herbal medicines Poria cocas, Glycyrrhiza uralensis, and Ulmus macrocarpa were reported to be parchymic acid, glabridin, and flavonoids, respectively. The aim of this study was to investigate the whitening and antioxidant effects of a mixture of P. cocas, G. uralensis, and U. macrocarpa extracts (PGUE) in B16F1 cells to develop whitening cosmetics. PGUE inhibited DPPH radicals and lipid peroxidation, in addition to high reduction power, compared with Glycyrrhiza uralensis ethylacetate extracts (GUEE). Furthermore, PGUE exhibited a protective effect against DNA oxidation induced by the hydroxyl radicals. In addition to its antioxidant activity, the inhibitory activity of PGUE against tyrosinase, which is associated with melanogenesis, was greater than that of arbutin used as a positive control. Moreover, PGUE exerted an inhibitory effect on melanin synthesis in live melanoma cells and reduced the expression levels of superoxide dismutase-1 (SOD-1) and tyrosinase related protein-1 (TRP-1). These results indicate that PGUE has skin whitening and antioxidant effects, suggesting that this mixture can be used as the main ingredient in the development of effective whitening cosmetics.

새로운 천식 표현형의 등장

권지원 ( Ji Won Kwon ),홍수종 ( Soo Jong Hong ) 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 2012 소아알레르기 및 호흡기학회지 Vol.22 No.2

Asthma is a complex and heterogeneous disease, which is comprised of seperate phenotypes sharing common characteristics, such as airway inflammation, bronchial hyperresponsiveness and variable airflow limitation. Traditionally, asthma phenotypes have been described by combinations of clinical characteristics, according to the expert s recommendation, but they are now focusing` on the pathobiologic mechanisms often using exploratory statistical methods. Several phenotypes and endotypes have been suggested by biased or unbiased phenotyping approaches. However, more detailed studies are still needed. In the future, more integrated large-scaled consortium of cohorts, including clinical information, genetics, molecular biology, and experiments will promote to understand the pathobiologic mechanisms of asthma phenotypes for the personalized therapy.