Yee-Jin Shin

Interaction between IL13 genotype and environmental factors in the risk for allergic rhinitis in Korean children

BACKGROUNDnThe prevalence of allergic rhinitis (AR) is increasing worldwide. Allergic diseases develop in susceptible subjects when they are exposed to specific environmental factors.nnnOBJECTIVEnWe analyzed changes in the prevalence of AR and identified genetic and environmental factors in early childhood that affect risk.nnnMETHODSnWe used the International Study of Asthma and Allergies in Childhood questionnaire to collect data on AR, allergies, and environmental exposures from 4554 elementary school students from 5 areas of Seoul, Korea, in 2008. We also obtained DNA from 1050 subjects from 1 area of Seoul for genotype analysis of IL13.nnnRESULTSnWe identified genetic and environmental factors during infancy and early childhood that increased the risk for current AR (resulting in a diagnosis of AR and AR symptoms in the past 12 months) in elementary school-aged children. These included allergic disease in parents and antibiotic use in infants, allergic disease in parents and exposure of infants to mold, and allergic disease in parents and moving an infant to a newly built house. The risk of current AR also increased in subjects with GA or AA at nucleotide 2044 in IL13 who had been exposed to mold in the home during infancy (adjusted odds ratio, 3.27; 95% CI, 1.75-6.11) compared with subjects who had GG at this position and had not been exposed to mold (adjusted odds ratio, 3.27; 95% CI, 1.75-6.11).nnnCONCLUSIONnThe prevalence of AR is increasing in Korean children. Children with a family history of allergic disease and exposure to specific environmental risk factors during infancy are more likely to have AR. Children with GA or AA at IL13(+2044) are at increased risk for AR when exposed to mold in the home during the first year of life.

Exposure to Gene-Environment Interactions before 1 Year of Age May Favor the Development of Atopic Dermatitis

Background: The aims of this study were to determine (1) the prevalence of atopic dermatitis (AD) in Seoul, Korea, and (2) the influence of environmental and genetic factors on disease risk. Methods: A questionnaire survey was conducted in 5,036 primary school children and 4,607 middle school children in 2008. For each child, a modified version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and a questionnaire assessing exposure to environmental variables were completed. Results: In primary school children, the lifetime prevalence of itchy eczema was 24.3%, the 12-month prevalence of itchy flexural eczema was 18.0%, the lifetime prevalence of AD diagnosis was 31.3%, and the 12-month prevalence of AD treatment was 14.5%. In middle school children, the corresponding rates were 16.0, 10.8, 22.1, and 8.3%, respectively. These rates are significantly higher than those reported in similar studies conducted in 1995 and 2000. In both primary and middle school children, a parental history of allergic disease and a history of having moved into a newly built house before 1 year of age were independently associated with a risk for current AD. For current AD, the prevalence odds ratio was higher in the subgroup with both a genetic and a specific environmental risk factor than in the subgroup with no risk factor or subgroups with only one risk factor. Conclusions: The prevalence of AD in primary and middle school children in Seoul has increased. Its development may be influenced by gene-environment interactions, particularly before 1 year of age.

Polymorphisms in GSDMA and GSDMB are associated with asthma susceptibility, atopy and BHR.

The gasdermin A (GSDMA) and gasdermin B (GSDMB) genes are located at 17q21.2. The GSDM family genes have been studied in the gastrointestinal tract but recent reports suggest that GSDMB is associated with childhood asthma in several populations. We investigated the association of the GSDMA and GSDMB variants with asthma in Korean children, and to assess the effect of these variants on intermediate phenotypes of asthma. Asthmatic (nu2009=u2009778) and normal (nu2009=u2009522) children were enrolled and genotypes were determined using PCR‐RFLP. Asthma susceptibility was associated with GG of the GSDMA (rs7212938) and TT of GSDMB (rs7216389). And a combination of risk alleles of two polymorphisms was associated with asthma susceptibility and a frequency of those was higher in asthmatic children with increased levels of total IgE (aOR 1.77, 95% CI 1.15–2.72) and BHR (aOR 1.54, 95% CI 0.99–2.40) compared to normal. Also, we observed a significant association between haplotype of two polymorphisms and asthma susceptibility. The region including the GSDMA and GSDMB polymorphisms may be associated with asthma susceptibility and intermediate phenotypes of asthma, such as elevated IgE and BHR, in Korean children with asthma. These results strongly support an important role for the GSDMA and GSDMB in the development of childhood asthma. Pediatr. Pulmonol. 2011; 46:701–708.

Prenatal maternal distress affects atopic dermatitis in offspring mediated by oxidative stress

BACKGROUNDnRecent evidence suggests that prenatal maternal distress increases the risk of allergic diseases in offspring. However, the effect of prenatal maternal depression and anxiety on atopic dermatitis (AD) risk remains poorly understood.nnnOBJECTIVEnWe investigated whether prenatal maternal distress is associated with AD risk in offspring and whether the mechanism is mediated by reactive oxygen species.nnnMETHODSnTwo general population-based birth cohorts formed the study. One cohort (Cohort for Childhood Origin of Asthma and Allergic Diseases [COCOA]) consisted of 973 mother-baby dyads, and the other (Panel Study on Korean Children [PSKC]) consisted of 1531 mother-baby dyads. The association between prenatal distress and AD was assessed by using Cox proportional hazards and logistic regression models. In COCOA placental 11β-hydroxysteroid dehydrogenase type 2 and glutathione levels and serum IgE levels in 1-year-old children were measured.nnnRESULTSnIn COCOA and PSKC AD occurred in 30.6% (lifetime prevalence) and 11.6% (1xa0year prevalence) of offspring, respectively. Prenatal maternal distress increased the risk of AD in offspring, both in COCOA (hazard ratio for depression, 1.31 [95% CI, 1.02-1.69]; hazard ratio for anxiety, 1.41 [95% CI, 1.06-1.89]) and PSKC (odds ratio for distress, 1.85 [95% CI, 1.06-3.25]). In COCOA both prenatal maternal depression and anxiety scores were positively related to the predicted probability of AD (Pxa0<xa0.001 in both). Prenatal distress decreased placental glutathione to glutathione disulfidexa0ratios (Pxa0=xa0.037) and, especially in those who later had AD, decreased placental 11β-hydroxysteroid dehydrogenase type 2 levels (Pxa0=xa0.010) and increased IgE levels at 1xa0year of age (Pxa0=xa0.005).nnnCONCLUSIONnPrenatal maternal depression and anxiety promote risk of AD in offspring. Maternal distress increases the predicted probability of AD. The mechanism might involve chronic stress, abnormal steroid levels, and reactive oxygen species.

The Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study: design, rationale and methods.

BackgroundThis paper describes the background, aim, and design of a prospective birth-cohort study in Korea called the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). COCOA objectives are to investigate the individual and interactive effects of genetics, perinatal environment, maternal lifestyle, and psychosocial stress of mother and child on pediatric susceptibility to allergic diseases.Methods/DesignThe participants in COCOA represents a Korean inner-city population. Recruitment started on 19 November, 2007 and will continue until 31 December, 2015. Recruitment is performed at five medical centers and eight public-health centers for antenatal care located in Seoul. Participating mother-baby pairs are followed from before birth to adolescents. COCOA investigates whether the following five environmental variables contribute causally to the development and natural course of allergic diseases: (1) perinatal indoor factors (i.e. house-dust mite, bacterial endotoxin, tobacco smoking, and particulate matters 2.5 and 10), (2) perinatal outdoor pollutants, (3) maternal prenatal psychosocial stress and the child’s neurodevelopment, (4) perinatal nutrition, and (5) perinatal microbiome. Cord blood and blood samples from the child are used to assess whether the child’s genes and epigenetic changes influence allergic-disease susceptibility. Thus, COCOA aims to investigate the contributions of genetics, epigenetics, and various environmental factors in early life to allergic-disease susceptibility in later life. How these variables interact to shape allergic-disease susceptibility is also a key aim.The COCOA data collection schedule includes 11 routine standardized follow-up assessments of all children at 6xa0months and every year until 10xa0years of age, regardless of allergic-disease development. The mothers will complete multiple questionnaires to assess the baseline characteristics, the child’s exposure to environmental factors, maternal pre- and post-natal psychological stress, and the child’s neurodevelopment, nutritional status, and development of allergic and respiratory illnesses. The child’s microbiome, genes, epigenetics, plasma cytokine levels, and neuropsychological status, the microbiome of the residence, and the levels of indoor and outdoor pollutants are measured by standard procedures.DiscussionThe COCOA study will improve our understanding of how individual genetic or environmental risk factors influence susceptibility to allergic disease and how these variables interact to shape the phenotype of allergic diseases.

A Korean syndrome of attachment disturbance mimicking symptoms of pervasive developmental disorder

Les variations de troubles de lattachement ont fait lobjet de bien peu dattention dans un contexte culturel. Cet article dcrit un syndrome clinique de 25 enfants koreens (âges de deux a quatre ans) qui ont presentes de serieux troubles de relations dattachement avec leurs modes de soin et dees problemes de developpement social et verbal, mimant dune certaine maniere les symptomes de trouble envahissant du developpement (Pervasive Developmental Disorder, en anglais). Les enfants navaient pas de passe de maltraitance severe ni de milieu familial chaotique. Plusieurs des enfants ont ete adresses en consultation au service externe de lHopital Universitaire de Yonsei, a Seoul en Koree, avec un diagnostic preliminaire dautisme. Des evaluations medicales et psychologiques detaillees ont ete faites et les resultats ont ete frappants. Les changements dans les symptomes des enfants ont commence a prendre place durant les evaluations et les difficultes dans les relations de mode de soin sont devens apparentes. Un sous-groupe de dix enfants a ete traite pendant une annee ou plus, avec des degres variables damelioration. Les particularites cliniques sont discutees en termes de certains facteurs contextuels et culturels koreens particuliers.

Prenatal maternal depression is associated with low birth weight through shorter gestational age in term infants in Korea

BACKGROUNDnMaternal prenatal depression is associated with lower offspring birth weight, yet the impact of gestational age on this association remains inadequately understood.nnnAIMSnWe aimed to investigate the effect of prenatal depression on low birth weight, gestational age, and weight for gestational age at term.nnnSTUDY DESIGNnProspective cohort study.nnnSUBJECTnData were collected from 691 women in their third trimester of pregnancy who went on to give birth to a singleton at term without perinatal complications. One hundred and fifty-two women had a Center for Epidemiologic Studies Depression Scale-10 score ≥10 and were classed as prenatally depressed.nnnOUTCOME MEASURESnLow birth weight (<2500g), gestational age at birth, and birth weight percentile for gestational age.nnnRESULTSnOffspring of prenatally depressed women were more likely to be low birth weight (Odds ratio [OR] 2.94, 95% confidence interval [CI] 1.14-7.58) than offspring of prenatally non-depressed women, but the association was attenuated (OR 1.66, 95% CI 0.55-5.02) when adjusted for gestational age. Offspring of prenatally depressed women had lower gestational age in weeks (OR for one week increase in gestational age: 0.66, 95% CI 0.47-0.93) than offspring of prenatally non-depressed women. There was no association between prenatal depression and birth weight percentile for gestational age.nnnCONCLUSIONSnPrenatal depression was not associated with low birth weight at term, but was associated with gestational age, suggesting that association between maternal depression and birth weight may be a reflection of the impact of depression on offspring gestational age.

Polymorphisms of the PTGDR and LTC4S influence responsiveness to leukotriene receptor antagonists in Korean children with asthma

Activation of the prostaglandin D2 receptor (PTGDR) may contribute to pulmonary vasodilation, bronchoconstriction, recruitment of eosinophils, basophils and T-lymphocytes, and enhanced synthesis of leukotriene C4. We investigated whether polymorphisms of the leukotriene C4 synthase (LTC4S) −444A/C and PTGDR −441T/C were associated with clinical phenotypes and responsiveness to leukotriene receptor antagonist (LTRA) in Korean asthmatic children. We enrolled 270 normal and 870 asthmatic children. We prescribed montelukast (5u2009mg per day) to 100 of asthmatic children, and analyzed the responsiveness to LTRA by exercise challenge tests. Polymorphisms were genotyped by PCR–restriction fragment length polymorphism. As the number of minor alleles of the PTGDR −441T/C and LTC4S −444A/C polymorphisms increased, the log total eosinophil counts increased in atopic asthmatic children (P-value=0.03). We found a significant association between responsiveness to montelukast and the PTGDR polymorphism (P-value=0.038). However, the LTC4S −444A/C and PTGDR −441T/C were not associated with the susceptibility for asthma (LTC4S, AA versus AC+CC, adjusted odds ratio of 0.98 (95% confidence interval, 0.73–1.31); PTGDR, TT versus TC+CC, adjusted odds ratio of 0.90 (95% confidence interval, 0.68–1.19)) or clinical phenotypes (P-value>0.05). The effects of the PTGDR and LTC4S polymorphisms on the enhancement of eosinophil counts were additive in the Korean children with asthma. In addition, the PTGDR polymorphism seems to be associated with the responsiveness to LTRA. Therefore, therapies that target the PTGDR may be useful for modulating the responsiveness to LTRA.

Parent‐reported ISAAC written questionnaire may underestimate the prevalence of asthma in children aged 10–12 years

The aim of the present study was to compare the validity of the International Study of Asthma and Allergies in Childhood (ISAAC) written (WQ) and audiovisual questionnaires (AVQ 3.0) in two age‐groups (10–12 and 13–15 years, respectively).

Patterns of Psychosocial Adaptation and Allergic Disorders in Korean Schoolchildren

Background: To date, there is little evidence to support an association between symptoms of pediatric allergic disorders and psychosocial factors in the general population, particularly in Asian countries. The current study aims to investigate the relationship between psychosocial factors and symptoms of allergic disorders and to investigate the association between behavior problems and biomarkers of atopy. Methods: A cross-sectional survey of parental responses to the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and the Korean version of the Child Behavior Checklist (CBCL) was conducted from one elementary school in Seoul, Korea. Skin prick tests for 18 major allergens were also performed. Results: A total of 780 children with valid CBCL surveys were included in the study. Externalizing problems were significantly larger in children with asthmatic symptoms, while internalizing problems were significantly larger in children with symptoms of both asthma and allergic rhinitis. Social adaptations were significantly lower in children with symptoms of allergic rhinitis and atopic dermatitis. Boys with more positive allergens via the skin prick tests showed larger internalizing problems. Conclusions: While school children with allergic symptoms have been reported to have more difficulties with psychosocial adaptation, the patterns of psychosocial problems varied somewhat according to the types of atopic disorder. There was a positive relationship between atopy and behavior problems, especially in boys.