SummaryObjectives The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires have shown that the prevalence of childhood asthma is increasing worldwide. Although Asian countries used to have lower prevalence rates of allergic disease than Western countries, this prevalence is increasing in several Asian countries. To determine whether the prevalence of childhood asthma is changing in Korean adolescents, we compared findings from nationwide cross-sectional surveys in 1995 and 2000 on populations of middle-school children using the Korean version of the ISAAC questionnaire. Methods We developed Korean versions of the ISAAC written (WQ) and video (AVQ) questionnaires for allergic diseases. In 1995, the enrolled population consisted of 15 481 children, ages 12-15, and encompassing all three grades in middle school, selected from 34 schools across the nation; the response rate was 97.3%. In 2000, 15 894 children were selected from 31 of the same schools, and the response rate was 96.4%. The SAS system version 8.0 was utilized for all statistical analyses. Results The WQ showed that the lifetime and 12-month prevalence of wheeze did not change from 1995 to 2000. While the 12-month prevalence rates of sleep disturbed by wheezing and night cough increased, the rates of severe attack of wheezing and exercise-induced wheeze did not change, over this period of time. The lifetime prevalence of asthma diagnosis, however, increased significantly, from 2.7% in 1995 to 5.3% in 2000, as did the 12-month prevalence of asthma treatment, from 1.0% in 1995 to 1.9% in 2000. The AVQ also showed increases in the lifetime and 12-month prevalence rates of wheeze at rest, exercise-induced wheeze, nocturnal wheeze, nocturnal cough, and severe wheeze over this period of time. These were especially because of significant increases in the Provincial cities of Korea. Interestingly, the 12-month prevalence of wheeze was consistently high in Cheju with low air pollution indices, whereas this rate was low in Ulsan and Ansan with very high air pollution indices. Risk factor analysis showed that body mass index (BMI), passive smoking, and living with a dog or cat, but not air pollution, were associated with higher risk of wheeze. Conclusions In the 5-year period from 1995 to 2000, the prevalence of asthma symptoms has increased in Korean adolescents, much of it because of increases in Provincial Centers. BMI, passive smoking, and living with a dog or cat are important risk factors. Environmental factors other than air pollution may be associated with increases in asthma, especially in Provincial Centers.

The genes involved in signal transduction are major candidates in association studies on affective disorders and responses to antidepressants. We investigated whether the C825T polymorphism of the b3 subunit of G protein (GNB3) gene is associated with the symptom severity or treatment response of major depressive disorders (MDDs) in a Korean sample of 106 MDD patients; our study also included 133 healthy controls. Hypertensive subjects were excluded from the study because association between GNB3 variants and hypertension has been reported in previous studies. We found significantly more carriers of the 825T allele in MDD patients than in normal controls (w 2 ¼ 6.37, P ¼ 0.012; OR ¼ 2.19, 95% CI 1.18-4.05). The T-allele carriers showed higher scores than those with the CC genotype in the baseline total and in some subcategories of the Hamilton Depression Rating Scale (Po0.05). We also found a statistically significant association between T-allele carriers and antidepressant treatment response (Po0.05). These results suggest that the T allele of the C825T polymorphism in the GNB3 gene is associated with MDD. It was also demonstrated that MDD patients bearing the T allele had a severe symptomatology and a better response to antidepressant treatment than patients without the T allele.

Epigenetic fields for cancerization are involved in development of human cancers, especially those associated with inflammation and multiple occurrences. However, it is still unclear when such field defects are formed and what component of inflammation is involved in induction of aberrant DNA methylation. Here, in a mouse colitis model induced by dextran sulfate sodium (DSS), we identified three CpG islands specifically methylated in colonic epithelial cells exposed to colitis. Their methylation levels started to increase as early as 8 weeks after DSS treatment and continued to increase until colon cancers developed at 15 weeks. In contrast to the temporal profile of DNA methylation levels, infiltration of inflammatory cells spiked immediately after the DSS treatment and then gradually decreased. Exposure of cultured colonic epithelial cells to DSS did not induce DNA methylation and it was indicated that inflammation triggered by the DSS treatment was responsible for methylation induction. To clarify components of inflammation involved, severe combined immunodeficiency (SCID) mice that lack functional T-and B-cells were similarly treated. Even in SCID mice, DNA methylation, along with colon tumors, were induced at the same levels as in their background strain of mice (C.B17). Comparative analysis of inflammation-related genes showed that Ifng, Il1b and Nos2 had expression concordant with methylation induction whereas Il2, Il6, Il10, Tnf did not. These results showed that an epigenetic field defect is formed at early stages of colitis-associated carcinogenesis and that functional T and B cells are non-essential for the formation.

Previous evidence suggests that the serotonin transporter gene (SLC6A4) is associated with the structure of brain regions that are critically involved in dysfunctional limbic-cortical network activity associated with major depressive disorder (MDD). Diffusion tensor imaging (DTI) and tract-based spatial statistics were used to investigate changes in white matter integrity in patients with MDD compared with healthy controls. A possible association between structural alterations in white matter tracts and DNA methylation of the SLC6A4 promoter region was also assessed. Thirty-five medication-naive patients with MDD (mean age: 40.34, male/female: 10/25) and age, gender and education level matched 49 healthy controls (mean age: 41.12, male/female: 15/34) underwent DTI. SLC6A4 DNA methylation was also measured at five CpG sites of the promoter region, and the cell type used was whole-blood DNA. Patients with MDD had significantly lower fractional anisotropy (FA) values for the genu of the corpus callosum and body of the corpus callosum than that in healthy controls (family-wise error corrected, P<0.01). Significant inverse correlations were observed between SLC6A4 DNA methylation and FA (CpG3, Pearson's correlation: r=−0.493, P=0.003) and axial diffusivity (CpG3, Pearson's correlation: r=−0.478, P=0.004) values of the body of the corpus callosum in patients with MDD. These results contribute to evidence indicating an association between epigenetic gene regulation and structural brain alterations in depression. Moreover, we believe this is the first report of a correlation between DNA methylation of the SLC6A4 promoter region and white matter integrity in patients with MDD.

Brain-derived neurotrophic factor (BDNF) is a candidate molecule for influencing the clinical response to antidepressant treatment. The aims of this study were to determine the relationship between the Val66Met polymorphism in the BDNF gene and the response to mirtazapine in 243 Korean subjects with major depressive disorder (MDD). The reduction in the Hamilton Depression score over the 8-week treatment period was not influenced by BDNF V66M genotypes. A marginal effect of genotype on somatic anxiety score was observed at baseline (P = 0.047 in the dominant model). However, genotype-time interaction had no effect on somatic anxiety score after the 8-week a treatment period. Plasma BDNF levels tended to increase during mirtazapine treatment, although without statistical significance (P = 0.055). After 8 weeks of mirtazapine treatment, plasma BDNF levels were higher in Met allele homozygotes (1499.7 ± 370.6 ng/mL) than in Val allele carriers (649.7 ± 158.5 ng/mL, P = 0.049). Our results do not support the hypothesis that the Val66Met promoter polymorphism in the BDNF gene influences the therapeutic response to mirtazapine in Korean MDD patients. However, our data indicate that this polymorphism results in increased plasma BDNF after mirtazapine treatment.