Impact of Radiofrequency Exposure From Mobile Phones on the Risk of Developing Brain Tumors in Korean and Japanese Adolescents: A MOBI-Kids Case-control Study.

BACKGROUND: This study aimed to examine the association between risk of brain tumors and radiofrequency (RF) exposure from mobile phones among young people in Korea and Japan. METHODS: This case-control study of brain tumors in young people was conducted in Korea and Japan under the framework of the international MOBI-Kids study. We included 118 patients diagnosed with brain tumors between 2011 and 2015 and 236 matched appendicitis controls aged 10-24 years. Information on mobile phone use was collected through face-to-face interviews. A detailed RF exposure algorithm, based on the MOBI-Kids algorithm and modified to account for the specificities of Japanese and Korean phones and networks, was used to calculate the odds ratios (ORs) for total cumulative specific energy using conditional logistic regression. RESULTS: The adjusted ORs in the highest tertile of cumulative call time at 1 year before the reference date were 1.61 (95% confidence interval [CI], 0.72-3.60) for all brain tumors and 0.70 (95% CI, 0.16-3.03) for gliomas, with no indication of a trend with exposure. The ORs for glioma specifically, were below 1 in the lowest exposure category. CONCLUSION: This study provided no evidence of a causal association between mobile phone use and risk of brain tumors as a whole or of glioma specifically. Further research will be required to evaluate the impact of newer technologies of communication in the future.

Exposure to Hazardous Substances and Their Health Effects Among Residents Living Near Three Industrial Waste Incinerators in Korea.

BACKGROUND: This study aimed to evaluate exposure to various hazardous substances emitted by incineration facilities and their likely effect on the health for residents of Bugi-myeon, Cheongju, Korea, which has three incineration facilities. METHODS: Heavy metals, polycyclic aromatic hydrocarbons (PAHs), and dioxin concentrations in the air and soil of exposed and control areas were measured. Moreover, the exposure levels to harmful substances and its effects on health were investigated in 1,124 exposed and 232 control adults. RESULTS: PAHs and dioxin concentrations in the air in the exposed area were significantly higher than in the control area. Urinary cadmium and PAHs metabolite concentrations were significantly higher in the exposed group than in the control group. The exposure group also had a higher prevalence of depression and self-reported allergic symptoms than the control group. CONCLUSION: The possibility of residents in Bugi-myeon being exposed to hazardous substances at incineration facilities cannot be ruled out. To prevent them from further exposure to hazardous substances, it is necessary to prohibit the expansion of additional incineration facilities in this area and to implement continuous monitoring projects for residents.

Effects of Environmental Cadmium Exposure on the Liver in Korean Adults: Cross-Sectional and Longitudinal Studies.

Cadmium (Cd) is a ubiquitous environmental pollutant with an exceptionally long biological half-life. The liver is a major organ for Cd metabolism, but the toxicity of Cd is unclear. This study sought to determine whether blood Cd (BCd) level (representing recent exposure [months] to Cd) was associated with liver function in Korean adults, both cross-sectionally and longitudinally. The baseline cross-sectional study involved 2,086 adults (male: 908, female: 1,178) in 2010 - 2011, and 503 of them (male: 207, female: 296) were followed up in 2014 - 2015. BCd was measured by graphite-furnace atomic absorption spectrometry, and liver function indices (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and γ-glutamyltransferase [GGT]) were determined. Liver damage was defined as an abnormal elevation of more than one liver function index. The geometric mean of BCd (1.07 µg/L) was higher in females than in males (1.16 vs. 0.96 µg/L). Liver function indices increased significantly in a dose-dependent manner according to the BCd levels, except for ALT in males, and were higher in males than in females. BCd level was also associated with the risk of liver damage in both sexes. No significant changes in BCd were observed between baseline and follow-up. The liver function indices in 2014 - 2015 were comparable to those in 2010 - 2011 in males, while ALT and GGT were significantly increased in 2014 - 2015 compared to 2010 - 2011 in females with relatively high BCd. These findings suggest that even a low level of environmental Cd exposure, short- and long-term, may affect liver function, and females appear more susceptible than males.

Association of indoor and outdoor short-term PM2.5 exposure with blood pressure among school children.

The association between particulate matter and children's increased blood pressure is inconsistent, and few studies have evaluated indoor exposure, accounting for time-activity. The present study aimed to examine the association between personal short-term exposure to PM2.5 and blood pressure in children. We conducted a panel study with up to three physical examinations during different seasons of 2018 (spring, summer, and fall) among 52 children. The indoor PM2.5 concentration was continuously measured at home and classroom of each child using indoor air quality monitors. The outdoor PM2.5 concentration was measured from the nearest monitoring station. We constructed a mixed effect model to analyze the association of short-term indoor and outdoor PM2.5 exposure accounting for time-activity of each participant with blood pressure. The average PM2.5 concentration was 34.3 ± 9.2 µg/m3 and it was highest in the spring. The concentration measured at homes was generally higher than that measured at outdoor monitoring station. A 10-µg/m3 increment of the up to previous 3-day mean (lag0-3) PM2.5 concentration was associated with 2.7 mmHg (95%CI = 0.8, 4.0) and 2.1 mmHg (95%CI = 0.3, 4.0) increases in systolic and diastolic blood pressure, respectively. In a panel study comprehensively evaluating both indoor and outdoor exposures, which enabled more accurate exposure assessment, we observed a statistically significant association between blood pressure and PM2.5 exposure in children.

Cancer risk in the residents of a town near three industrial waste incinerators in Korea: a retrospective cohort study.

BACKGROUND: Three industrial waste incinerators (IWIs) were built in 1999, 2001, and 2010, within a 3 km radius of a town with a population of around 5000 in Korea. This study evaluated whether residents near these three IWIs had increased cancer incidence than those from other areas in Korea using regional health data. METHODS: Standardized incidence ratios (SIR) were calculated using the frequency of cancer cases in the National Cancer Registry of the exposed area (Buki-myeon), Chungcheongbuk-do (Chungbuk, state including Buki-myeon), and whole Korea from 1999 to 2017. A retrospective cohort was created using National Health Insurance System data from 2002 to 2018. The exposed group was defined as those having a residential history in the exposed area. The control group was defined as those having a residential history in nearby towns or counties in Chungbuk, excluding counties having living and cultural areas in other provinces and cities. Hazard ratio (HR) and 95% confidence intervals (CI) were estimated using the Cox proportional hazard model adjusted for age, level of health insurance fee, and smoking history. RESULTS: In the ecological study using National Cancer Registry data, the risk of all cancers, all cancers excluding thyroid, esophageal, stomach, and lung cancers in the exposed area were 1.13 (95% CI 1.03-1.24), 1.15 (95% CI 1.04-1.26), 1.91 (95% CI 1.13-2.89), 1.39 (95% CI 1.14-1.66), and 1.29 (95% CI 1.03-1.57) times higher than in whole Korea among exposed males, respectively. In the retrospective cohort, 4300 males (26,821 person-years) and 3796 females (24,746 person-years) in exposed group, 150,964 males (1,212,010 person-years) and 134,535 females (1,104,025 person-years) in control group were analyzed. After adjusting for several confounding factors, the risks for gallbladder cancer among males and kidney cancer among females were 2.65 (95% CI 1.38-5.06) and 2.82 (95% CI 1.13-7.03) times higher in the exposed group versus the control group, respectively. CONCLUSIONS: Cancer risk was higher in Koreans having residential history living near IWIs compared to the other areas. Further study warrants nationwide effects and longer follow-up of WIs for cancers in Korea.

Exposure Levels and Contributing Factors of Various Arsenic Species and Their Health Effects on Korean Adults.

Arsenic is a human carcinogen. Data on urinary arsenic species analyses of Koreans are limited. This study evaluated the arsenic exposure level, contributing factors, and health effects in Korean adults. Dietary intake information and urine samples were obtained from 2044 participants. Arsenic exposure was assessed based on urinary concentrations of arsenic species, such as inorganic arsenic, As(III) and As(V), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and arsenobetaine (AsB), using high-performance liquid chromatography with inductively coupled plasma mass spectrometry, followed by determination of biomarkers, malondialdehyde and c-peptide. The geometric mean concentrations were 30.9 µg/L for the sum of inorganic arsenic and their metabolites, and 84.7 µg/L for the total sum of arsenic measured. Urinary concentrations of arsenic species were influenced by age, inhabitant area (inland or coastal), and seafood intake, which was positively correlated with inorganic arsenic, DMA, and AsB. Rice intake was positively correlated with inorganic arsenic and its metabolites but not with AsB. Additionally, malondialdehyde and c-peptide levels were significantly associated with urinary concentrations of various arsenic species. Seafood and rice are major sources of organic/inorganic arsenic exposure in Korean adults; however, it is necessary to evaluate whether their overconsumption could have a potentially detrimental effect on human health.

Mobile Phone Use and Time Trend of Brain Cancer Incidence Rate in Korea.

This study evaluated the time trends in mobile phone subscriber number by mobile network generation (G) and brain cancer incidence by type in Korea. We obtained data from the Information Technology Statistics of Korea (1984-2017) and Korea Central Cancer Registry (1999-2017). The average annual percent change was estimated using Joinpoint regression analysis. We evaluated 29,721 brain cancer cases with an age-standardized incidence rate (ASR) of 2.89/100,000 persons. The glioma and glioblastoma annual ASR significantly increased in 2.6% and 3.9% of males and 3.0% and 3.8% of females, respectively. The ASR for frontal lobe involvement was the highest. The ASR of gliomas of unspecified grade annually increased by 7.8%; those for unspecified topology and histology decreased. The incidence of glioma, glioblastoma, frontal, temporal, and high-grade glioma increased among those aged ≥60 years. No association was observed between the mobile phone subscriber number and brain cancer incidence in Korea. Furthermore, long-term research is warranted because of the latency period of brain cancer. © 2021 Bioelectromagnetics Society.

Association between exposure to traffic-related air pollution and pediatric allergic diseases based on modeled air pollution concentrations and traffic measures in Seoul, Korea: a comparative analysis.

BACKGROUND: Pediatric allergic diseases are a major public health concern, and previous studies have suggested that exposure to traffic-related air pollution (TRAP) exposure is a risk factor. These studies have typically assessed TRAP exposure using traffic measures, such as distance to major roads, or by modeling air pollutant concentrations; however inconsistent associations with pediatric allergic diseases have often been found. Using road proximity and density, we previously found an association between TRAP and atopic eczema among approximately 15,000 children living in Seoul, Korea, heavily populated and highly polluted city in which traffic is a major emission source. We aimed to conduct a parallel analysis using modeled air pollution concentrations and thus examine the consistency of the association. Specifically, we examined the associations of individual-level annual-average concentrations of NO2, PM10, and PM2.5 with symptoms and diagnoses of three pediatric allergic diseases including asthma, allergic rhinitis, and atopic eczema. METHODS: The study population included 14,614 children from the Seoul Atopy Friendly School Project Survey in Seoul, Korea, in 2010. To assess individual exposures to TRAP among these children, we predicted annual-average concentrations of NO2, PM10, and PM2.5 at the children's home addresses in 2010 using universal kriging and land use regression models along with regulatory air quality monitoring data and geographic characteristics. Then, we estimated odds ratios (ORs) of the three allergic diseases for interquartile increases in air pollution concentrations after adjusting for individual risk factors in mixed effects logistic regression. RESULTS: Symptoms and diagnoses of atopic eczema symptoms showed an association with NO2 (OR = 1.07, 95% confidence interval = 1.02-1.13; 1.08, 1.03-1.14) and PM10 (1.06, 1.01-1.12; 1.07, 1.01-1.13). ORs of PM2.5 were positive but not statistically significant (1.01, 0.95-1.07; 1.04, 0.98-1.10). No association was found between asthma and allergic rhinitis, although PM2.5 showed a marginal association with allergic rhinitis. CONCLUSIONS: Our consistent findings regarding the association between TRAP and the prevalence of atopic eczema using traffic measures and surrogate air pollutants suggested the effect of TRAP on children's health. Follow-up studies should elucidate the causal link, to support subsequent policy considerations and minimize adverse health effects in children.

Epidemiological Characteristics of COVID-19 Outbreak at Fitness Centers in Cheonan, Korea.

BACKGROUND: In February 2020, a coronavirus disease 2019 (COVID-19) outbreak was reported in fitness centers in Cheonan, Korea. METHODS: From February 24 to March 13, an epidemiological investigation was conducted on the fitness center outbreak. All those who were screened were tested for severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) using real-time reverse transcriptase polymerase chain reaction. Contacts were traced and self-isolated for 14 days. We determined the epidemiological characteristics of confirmed cases of SARS-CoV-2 infection, and estimated the time-dependent reproduction number to assess the transmission dynamics of the infection. RESULTS: A total of 116 cases were confirmed, and 1,687 contacts were traced. The source cases were 8 Zumba instructors who led aerobics classes in 10 fitness centers, and had the largest average number of contacts. A total of 57 Zumba class participants, 37 of their family members, and 14 other contacts were confirmed as cases. The attack rate was 7.3%. The contacts at Zumba classes and homes had a higher attack rate than other contacts. The mean serial interval (± standard deviation) were estimated to be 5.2 (± 3.8) days. The time-dependent reproduction number was estimated to be 6.1 at the beginning of the outbreak, but it dropped to less than 1, 2 days after the epidemiological investigation was launched. CONCLUSION: The results suggest that the COVID-19 outbreak was effectively contained with rigorous contact tracing, isolating, and testing in combination with social distancing without a lock-down.

Prenatal particulate matter affects new asthma via airway hyperresponsiveness in schoolchildren.

BACKGROUND: The most relevant time of PM10 exposure to affect airway hyperresponsiveness (AHR) and new development of asthma in school-aged children is unclear. The aims of this study were to investigate the most critical time of PM10 exposure to affect AHR and new diagnosis of asthma from AHR in school-aged children. METHODS: Elementary schoolchildren (n = 3570) have been enrolled in a nationwide prospective 4-year follow-up survey in Korea from 2005 to 2006. Individual annual PM10 exposure was estimated by using an ordinary kriging method from the prenatal period to 7 years of age. AHR at 7 years was defined by a methacholine PC20 ≤8 mg/mL. RESULTS: PM10 exposure during pregnancy and at 1 year of age showed significant effects on AHR (aOR: 1.694, 95% CI: 1.298-2.209; and aOR: 1.750, 95% CI: 1.343-2.282, respectively). PM10 exposure during pregnancy was associated with the risk of a new diagnosis of asthma (aOR: 2.056, 95% CI: 1.240-3.409), with the highest risk in children with AHR at age 7 (aOR: 6.080, 95% CI: 2.150-17.195). PM10 exposure in the second trimester was associated with the highest risk of a new diagnosis of asthma in children with AHR at age 7 (aOR: 4.136, 95% CI: 1.657-10.326). CONCLUSIONS: Prenatal PM10 exposure in the second trimester is associated with an increased risk of a new diagnosis of asthma in school-aged children with AHR at 7 years. This study suggests that PM10 exposure during a specific trimester in utero may affect the onset of childhood asthma via AHR.

Effects of traffic-related air pollution on susceptibility to infantile bronchiolitis and childhood asthma: A cohort study in Korea.

OBJECTIVE: This study examined the role of exposure to traffic-related air pollution (TRAP) on susceptibility to asthma in children with past episodes of bronchiolitis. METHODS: The baseline data included 2,627 school children aged 6-14 years who had participated in the longitudinal follow-up survey of the Children's Health and Environmental Research of Korea. Lifetime wheezing, past episodes of bronchiolitis, and doctor-diagnosed asthma were evaluated using an International Study of Asthma and Allergies in Childhood questionnaire. We used generalized linear regression with binomial distribution to calculate the relative risk (RR) between TRAP, assessed by proximity to a main road and the total length of roads, and asthma. RESULTS: Compared with the subjects who had less than 100 m of road length within 200-m radius from their home, those with more than 500 m of road length had significantly increased odds for infantile bronchiolitis (adjusted OR [aOR]: 1.57, 95% confidence interval [CI]: 1.01-2.42). Positive exposure-response relationships were found between residential proximity to the main road and asthma (aOR: 1.79, 95% CI: 1.05-3.06; <75 m vs. >700 m from a main road, P for the trend = 0.02). Closer residential proximity to the main road (<75 m) and bronchiolitis combined increased the risks of newly diagnosed asthma (adjusted RR: 3.62, 95% CI: 1.07-12.26) compared with those without bronchiolitis and living ≥ 75 m away from the main road. CONCLUSIONS: TRAP appeared to be associated with an increased asthma among children with bronchiolitis, indicating the importance of modifying effects of bronchiolitis in asthma pathogenesis.

Associations between urinary cotinine and symptoms of attention deficit/hyperactivity disorder and autism spectrum disorder.

BACKGROUND: The present study investigated associations between urinary cotinine levels as a biomarker of secondhand smoke exposure and symptoms of attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). METHODS: A total of 520 child participants (200 with ADHD, 67 with ASD, and 253 normal control subjects) were assessed using the Korean version of the ADHD rating scale (K-ARS), Autism spectrum screening questionnaire (ASSQ), and Behavioral Assessment System for Children, second edition (BASC-2). The Korean version of the computer-based continuous performance test was used to assess cognitive function. Urinary cotinine was evaluated as a biomarker of secondhand smoke exposure. RESULTS: Urinary cotinine levels were significantly and positively associated with K-ARS score (B = 4.00, p < 0.001), ASSQ score (B = 1.71, p = 0.030), the behavioral problem subscales of the BASC-2 (B = 1.68-3.52, p < 0.001-0.045), and omission and commission errors in the continuous performance test (B = 6.21-8.42, p < 0.001-0.019). Urinary cotinine levels were also associated with the increased odds ratio of ADHD (OR = 1.55, 95% CI 1.05-2.30, p = 0.028) and ASD (OR = 1.89, 95% CI 1.12-3.21, p = 0.018). CONCLUSION: Urinary cotinine levels were associated with lower behavioral adaptation and cognitive function and increased odds ratios of ADHD and ASD, indicating a negative effect of secondhand smoke exposure on the symptomatic manifestation of ADHD and ASD.

Associations between attention-deficit/hyperactivity disorder symptoms and dietary habits in elementary school children.

OBJECTIVE: The aim of the present study was to investigate the associations between dietary habits and attention deficit/hyperactivity disorder (ADHD) symptoms in elementary school children. METHODS: The parents of 16,831 participating children assessed the ADHD symptoms of their children by responding to the Korean version of the ADHD rating scale (K-ARS). Parents also responded to the food habit questionnaire, which consists of 8 items regarding the eating pace, the frequency of overeating, and patterns of eating six types of food: fast food, soft drinks, instant noodles, fruit and vegetables, and milk. RESULTS: K-ARS scores were positively associated with higher consumption of foods categorized as unhealthy, including fast food, soft drinks, and instant noodles, and negatively associated with higher consumption of fruit and vegetables categorized as healthy foods. K-ARS scores were also higher in the groups who overate more frequently and ate faster or slower compared to other family members. CONCLUSION: Our findings may provide useful clinical information for dietary interventions in children with ADHD.

Environmental Tobacco Smoke Exposure at Home and Attributable Problem Behaviors in Korean Children and Adolescents for 2012-2014 in a Nationally Representative Survey.

BACKGROUND: This study aimed to examine the environmental tobacco smoke (ETS) exposure at home and associated problem behaviors in Korean children and adolescents. METHODS: Approximately 2,167 children aged 3-18 years were included in the study after excluding 163 active smokers from the Korean Environmental Health Survey in Children and Adolescents (2012-2014). ETS data were obtained using a questionnaire; problem behaviors were measured using the Child Behavior Checklist administered to parents. The relationship between ETS exposure and problem behavior was evaluated using a survey regression model adjusted for region, age, sex, income, and father's education. The population-attributable fraction (PAF%) was calculated based on problem behaviors related to ETS exposure at home. RESULTS: The rates of ETS exposure at home were 20%, 28%, and 39% in children aged 3-5, 6-11, and 12-18 years, respectively; ETS exposure at home was associated with behavioral problems: the exposed group having higher total behavioral problem score (95% confidence interval [CI]) than the non-exposed by 2.46 (0.60-4.32) and 2.74 (0.74-4.74) in children aged 6-11 and 12-18 years, respectively, with no significant association in those aged 3-5 years. The PAF% (95% CI) of total problem behaviors for ETS exposure at home were 2.68 (-10.11-17.78), 10.66 (3.25-17.55), and 11.62 (3.03-18.96) in children aged 3-5, 6-11, and 12-18 years, respectively. Children with externalizing problems had higher PAF% than those with internalizing problems. CONCLUSION: In Korea, ETS exposure at home is associated with problem behaviors in children and adolescents with about more than 10% population attributable fraction.

Lead, Mercury, and Cadmium Exposure in the Korean General Population.

BACKGROUND: Lead (Pb), mercury (Hg), and cadmium (Cd) are well-known environmental pollutants. They are unnecessary in the biological processes of humans. This study was performed to estimate the representative background exposure levels to the metals by measuring concentrations in whole blood of the Korean general population. METHODS: This population-based cross-sectional study included 4,000 subjects (1,886 males and 2,114 females) 0-83 years of age in 2010 and 2011. Adult subjects (≥ 19 years of age) were collected by sex- and age-stratified probability method, and preschool- and school-aged subjects were recruited by a cluster sampling method. Written consent was provided prior to blood sampling. Pb and Cd blood concentrations were determined by a flameless atomic absorption spectrophotometry, and blood Hg was analyzed by a direct Hg analyzer. RESULTS: The geometric mean, median and 95th percentile of blood Pb was 1.82 µg/dL, 1.83 µg/dL, and 3.78 µg/dL, respectively. The respective values were 2.92 µg/L, 2.87 µg/L, 9.12 µg/L for Hg, and 0.56 µg/L, 0.59 µg/L, 2.20 µg/L for Cd. Blood Pb and Hg were higher in males than in females, but no sex difference was observed, respectively, in subjects 0-4 years of age for Pb and in subjects less than 20 years for Hg. However, blood Cd was higher in females than in males and no sex difference was observed in subjects < 30 years of age. CONCLUSION: This study provides representative data of human exposure to Pb, Hg, and Cd covering whole age groups of the general population in Korea.

Exposure amount and timing of solar irradiation during pregnancy and the risk of sensitization in children.

BACKGROUND: Solar irradiation affects sensitization to aeroallergens and the prevalence of allergic diseases. Little is known, however, about how the time and amount of solar irradiation during pregnancy affects such risks in children. We aimed to find out how solar irradiation during pregnancy affects sensitization to aero-allergens and the prevalence of allergic diseases in children. METHODS: This population-based cross-sectional study involved 7301 aged 6 years and aged 12 years children. Maternal exposure to solar irradiation during pregnancy was evaluated using data from weather stations closest to each child's birthplace. Monthly average solar irradiation during the second and third trimesters was calculated with rank by quartiles. Risks of allergic sensitization and allergic disease were estimated. RESULTS: Relative to the first (lowest) quartile, the adjusted odds ratio (aOR) for allergic sensitization in the fourth (highest) quartile was lowest within solar irradiation during pregnancy months 5-6 (aOR = 0.823, 95% CI 0.720-0.942, p < 0.05). During months 9-10, the aOR for allergic sensitization for the fourth was higher than the first quartile of solar irradiation (aOR = 1.167, 95% CI 1.022-1.333, p < 0.05). Similar results were observed when solar irradiation was analyzed as a continuous variable during months 5 (aOR = 0.975, 95% CI 0.962-0.989, p < 0.001) and month 9 (aOR = 1.018, 95% CI 1.004-1.031, p = 0.003). Increased solar irradiation during months 7-8 increased the risk of asthma (aOR = 1.309, 95% CI 1.024-1.674, p = 0.032). CONCLUSIONS: Maternal exposure to solar irradiation during the second trimester of pregnancy associated with reduced aeroallergen sensitization, whereas solar irradiation during the third trimester was related to increased sensitization to aeroallergens.

Association of Monoamine Oxidase A (MAOA) Gene uVNTR and rs6323 Polymorphisms with Attention Deficit and Hyperactivity Disorder in Korean Children.

Objective: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. The genetic cause of ADHD is still unclear, but the dopaminergic, serotonergic, and noradrenergic pathways have shown a strong association. In particular, monoamine oxidase A (MAOA) plays an important role in the catabolism of these neurotransmitters, suggesting that the MAOA gene is associated with ADHD. Therefore, we evaluated the relationship between the MAOA gene polymorphisms (uVNTR and rs6323) and ADHD. Materials and methods: We collected a total of 472 Korean children (150 ADHD cases and 322 controls) using the Korean version of the Dupaul Attention Deficit Hyperactivity Disorder Rating Scales (K-ARS). Genotyping was performed by PCR and PCR-RFLP. The Behavior Assessment System for Children Second Edition (BASC-2) was used to evaluate the problem behaviors within ADHD children. Results: We observed significant associations between the rs6323 and ADHD in girls (p < 0.05) and the TT genotype was observed as a protective factor against ADHD in the recessive model (OR 0.31, 95% CI 0.100⁻0.950, p = 0.022). The 3.5R-G haplotype showed a significant association in ADHD boys (p = 0.043). The analysis of subtype also revealed that the 4.5R allele of uVNTR was a risk factor for the development of ADHD in the combined symptom among girls (OR 1.87, 95% CI 1.014⁻3.453, p = 0.031). In the BASC-2 analysis, the MAOA uVNTR polymorphism was associated with activities of daily living in ADHD boys (p = 0.017). Conclusion: These results suggest the importance of the MAOA gene polymorphisms in the development of ADHD in Korean children. A larger sample set and functional studies are required to further elucidate of our findings.

Association of atopy phenotypes with new development of asthma and bronchial hyperresponsiveness in school-aged children.

BACKGROUND: Although previous studies have investigated the association between atopy phenotypes and allergic diseases, atopy characterizations in association with the development of allergic diseases remain poorly understood. OBJECTIVE: To identify atopy phenotypes in school-age children and to evaluate the association between atopy phenotypes and allergic diseases. METHODS: We enrolled 616 children with atopy defined as 1 or more positive allergen responses on skin prick tests and 665 children without atopy from the Children's Health and Environmental Research (CHEER) study. All children were followed up for 4 years at 2-year intervals. Atopy phenotypes were classified using latent class analysis. RESULTS: Four atopy phenotypes were characterized: later sensitization to indoor allergens (cluster 1); multiple early sensitization (cluster 2); early sensitization to outdoor allergens, especially Alternaria, and later sensitization to indoor allergens, including Aspergillus (cluster 3); and early sensitization to indoor allergens and later sensitization to outdoor allergens (cluster 4). New cases of asthma during follow-up were increased in clusters 2 and 3 (adjusted odds ratio [aOR], 2.76 and 4.25, respectively). The risk of new-onset bronchial hyperresponsiveness was highest in cluster 3 (aOR, 5.03). Clusters 2 and 4 had an increased risk of allergic rhinitis (aOR, 7.21 and 2.37, respectively). CONCLUSION: Identification of atopy phenotypes facilitates prediction of the development of asthma and bronchial hyperresponsiveness in school-age children. Our study suggests prevention of additional sensitization is required to modify the progression of allergic diseases.

Secondhand Smoke Exposure and Low Blood Lead Levels in Association With Attention-Deficit Hyperactivity Disorder and Its Symptom Domain in Children: A Community-Based Case-Control Study.

AIM: Secondhand smoke (SHS) is a major indoor pollutant. We examined the possible association between exposure to both SHS and low levels of lead and attention-deficit-hyperactivity disorder (ADHD) and its symptom domain in children. METHODS: This case-control study was based on the results of a community survey using the ADHD rating scale conducted in 49 elementary schools. Both cases and control subjects were confirmed by a child psychiatrist. Each case was matched with one control subject according to gender, school, and grade in school. Using a multivariate conditional logistic regression model, we analyzed 214 case-control pairs of children who ranged in age from 6 to 10 years. Urine and blood levels of cotinine and of lead were determined, and information pertaining to SHS exposure was obtained by means of a questionnaire. RESULTS: Exposure to low levels of lead (geometric mean = 1.65 µg/dL) was related to ADHD, particularly inattention (odds ratio [OR] = 1.67, 95% confidence interval [CI] = 1.07-2.59), whereas SHS exposure was associated mainly with hyperactivity/impulsivity (OR = 3.85, 95% CI = 1.55-9.56). In the pathway from blood lead to hyperactivity/impulsivity, children's SHS exposure mediated and indirectly accounted for about 73% of this relationship. The combined exposure to lead and SHS synergistically increased the risk of ADHD, evident as both inattention and hyperactivity/impulsivity. CONCLUSION: SHS, which is associated with hyperactivity/impulsivity in particular, combined with exposure to low blood levels of lead synergistically increased the risk of ADHD. Therefore, the exposure of children to both SHS and lead needs to be reduced. IMPLICATIONS: Although exposure to low levels of lead has been shown to be associated with ADHD, there is little evidence of symptom domain specificity. In our study, low blood lead levels were related to inattention. In addition, prenatal or postnatal exposure to SHS increased the risk of ADHD, particularly hyperactivity/impulsivity. Combined exposure to lead and SHS synergistically increased the risk for both these ADHD symptom domains. To protect children from environmental risk factors related to ADHD, it is necessary to further reduce children's exposure to SHS and lead, even in those with low blood lead levels.

Exome-wide association study identifies genetic polymorphisms of C12orf51, MYL2, and ALDH2 associated with blood lead levels in the general Korean population.

BACKGROUND: Lead (Pb) is a ubiquitous toxic metal present in the environment that poses adverse health effects to humans. Inter-individual variation in blood Pb levels is affected by various factors, including genetic makeup. However, limited data are available on the association between genetic variation and blood Pb levels. The purpose of this study was to identify the genetic markers associated with blood Pb levels in the Korean population. METHODS: The study subjects consisted of 1,483 healthy adults with no history of occupational exposure to Pb. We measured blood Pb levels and calculated probable daily intake of Pb according to dietary data collected using 24-hour recall. We conducted exome-wide association screening using Illumina Human Exome-12v1.2 platform (n = 500) and a replication analysis using VeraCode Goldengate assay (n = 1,483). RESULTS: Among the 244,770 single nucleotide polymorphisms (SNPs) tested, 12 SNPs associated with blood Pb level were identified, with suggestive significance level (P < 1 × 10-4). In the Goldengate assay for replication, three SNPs (C12orf51 rs11066280, MYL2 rs12229654, and ALDH2 rs671) were associated with statistically suggestively significant differences in blood Pb levels. When stratified by drinking status, a potential association of C12orf51 rs11066280, MYL2 rs12229654, and ALDH2 rs671 with blood Pb level was observed only in drinkers. A marginally significant gene-environment interaction between ALDH2 rs671 and alcohol consumption was observed in relation to blood Pb levels. The effects of the three suggestively significant SNPs on blood Pb levels was dependent on daily calcium intake amounts. CONCLUSIONS: This exome-wide association study indicated that C12orf51 rs11066280, MYL2 rs12229654, and ALDH2 rs671 polymorphisms are linked to blood Pb levels in the Korean population. Our results suggest that these three SNPs are involved in the determination of Pb levels in Koreans via the regulation of alcohol drinking behavior, and that their negative effects may be compensated by appropriate calcium intake.