To determine the factors responsible for the dramatic increase in the prevalence of diabetes in Korea. A computerized literature survey was conducted to evaluate the risk factors for Type 2 diabetes mellitus (T2DM) in Korea, including genome-wide association studies. National Statistics gross national income data was integrated with the reported prevalence of diabetes to evaluate the relationship between diabetes and the economic growth. The strength of the association was evaluated using measures of effect size, such as odds ratio and relative risks. The putative risk factors identified in Korean studies are very similar to the risk factors identified from the other countries, including genetic background. Genome-wide association studies reported relative risks of 1.5 or less, indicating that no single gene is associated with the risk of T2DM. The scientific evidence suggests that the dramatic increase in the incidence and prevalence of T2DM in Korea is related to the economic development of Korea, which has a direct influence on health policy, as well as an individual's health behaviors. We expect to observe the current diabetes incidence rates until the key risk factors are present for long enough in our society, at which point we would expect to start observing a more gradual increase in both the incidence and prevalence of T2DM in Korea.
Diabetes Mellitus, Type 2 ; Economic Development ; Genome-Wide Association Study ; Health Behavior ; Health Policy ; Incidence ; Korea ; Odds Ratio ; Prevalence ; Risk Factors

To determine the factors responsible for the dramatic increase in the prevalence of diabetes in Korea. A computerized literature survey was conducted to evaluate the risk factors for Type 2 diabetes mellitus (T2DM) in Korea, including genome-wide association studies. National Statistics gross national income data was integrated with the reported prevalence of diabetes to evaluate the relationship between diabetes and the economic growth. The strength of the association was evaluated using measures of effect size, such as odds ratio and relative risks. The putative risk factors identified in Korean studies are very similar to the risk factors identified from the other countries, including genetic background. Genome-wide association studies reported relative risks of 1.5 or less, indicating that no single gene is associated with the risk of T2DM. The scientific evidence suggests that the dramatic increase in the incidence and prevalence of T2DM in Korea is related to the economic development of Korea, which has a direct influence on health policy, as well as an individual's health behaviors. We expect to observe the current diabetes incidence rates until the key risk factors are present for long enough in our society, at which point we would expect to start observing a more gradual increase in both the incidence and prevalence of T2DM in Korea.
Diabetes Mellitus, Type 2 ; Economic Development ; Genome-Wide Association Study ; Health Behavior ; Health Policy ; Incidence ; Korea ; Odds Ratio ; Prevalence ; Risk Factors

Abnormal hematological values are associated with various disorders including cancer and cardiovascular, metabolic, infectious, and immune diseases. We report the copy number variations (CNVs) in clinically relevant hematological parameters, including hemoglobin level, red and white blood cell counts, platelet counts, and red blood cell (RBC) volume. We describe CNVs in several loci associated with these hematological parameters in 8,842 samples from Korean population-based studies. The data that we evaluated included four RBC parameters, one platelet parameter, and one associated with total white blood cell (WBC) count, exceeding the genome-wide significance. We show that CNVs in hematological parameters are associated with some loci, different from previously associated loci reported in single nucleotide polymorphism (SNP) association studies.
Blood Cell Count ; Blood Platelets ; Coat Protein Complex I ; Erythrocytes ; Genome-Wide Association Study ; Hemoglobins ; Immune System Diseases ; Leukocyte Count ; Leukocytes ; Platelet Count ; Polymorphism, Single Nucleotide

Neck pain is a common musculoskeletal condition, which causes substantial medical cost. In Korea, prevalence of neck pain in community based population, especially in elderly subjects, has scarcely been reported. We evaluated the prevalence, the severity and the risk factors of neck pain in elderly Korean community residents. Data for neck pain were collected for 1,655 subjects from a rural farming community. The point, 6-months and cumulative lifetime prevalence of neck pain was obtained in addition to the measurement of the severity of neck pain. The mean age of the study subjects was 61 yr and 57% were females. The lifetime prevalence of neck pain was 20.8% with women having a higher prevalence. The prevalence did not increase with age, and the majority of individuals had low-intensity/low-disability pain. Subjects with neck pain had a significantly worse SF-12 score in all domains except for mental health. The prevalence of neck pain was significantly associated with female gender, obesity and smoking. This is the first large-scale Korean study estimating the prevalence of neck pain in elderly population. Although the majority of individuals had low-intensity/low-disability pain, subjects with neck pain had a significantly worse SF-12 score indicating that neck pain has significant health impact.
Adult ; Aged ; Asian Continental Ancestry Group ; Female ; Humans ; Male ; Mental Health ; Middle Aged ; Neck Pain/complications/*epidemiology ; Obesity/complications/diagnosis ; Odds Ratio ; Prevalence ; Questionnaires ; Republic of Korea/epidemiology ; Risk Factors ; Rural Population ; Severity of Illness Index ; Sex Factors ; Smoking

In a murine model of systemic lupus erythematosus (SLE)-like chronic graft-versus-host disease (cGVHD), donor CD8+T cells rapidly fall into anergy to host cells, while donor CD4+T cells hyperactivate B cells and break B-cell tolerance to self-Ags in the recipient mouse. The functional recovery of donor CD8+T cells can result in the conversion of cGVHD to acute GVHD (aGVHD), indicating that donor CD8+T-cell anergy is a restriction factor in the development of cGVHD. In this report, we present evidence that donor CD4+CD25+regulatory T cells (T(reg) cells) are critical in maintaining the donor CD8+T-cell anergy and thus suppressing the development of aGVHD in mice that are naturally prone to cGVHD. Our results provide a novel insight into the role of T(reg) cells in determining cGVHD versus aGVHD.
T-Lymphocytes, Regulatory/*immunology ; Mice, Inbred DBA ; Mice ; Interleukin-2 Receptor alpha Subunit/*metabolism ; Immune Tolerance/physiology ; Graft vs Host Disease/*immunology ; Female ; Clonal Anergy/*physiology ; Chronic Disease ; CD8-Positive T-Lymphocytes/*immunology ; CD4-Positive T-Lymphocytes/*immunology ; Animals

BACKGROUND/OBJECTIVES: It is well-known that alcohol consumption is associated with stroke risk as well as with aldehyde dehydrogenase 2 gene (ALDH2) polymorphisms. However, it is unclear whether ALDH2 polymorphisms are associated with stroke risk independent of alcohol consumption and whether such association is modified by sex. We evaluated sex-specific associations of a common ALDH2 polymorphism and alcohol consumption with stroke risk in a Korean population. SUBJECTS/METHODS: We conducted a prospective cohort study involving 8,465 men and women, aged 40-69 years and free of stroke between June, 2001 and January, 2003, and followed for the development of stroke. We identified new cases of stroke, which were self-reported or ascertained from vital registration data. Based on genome-wide association data, we selected a single-nucleotide polymorphism (rs2074356), which shows high linkage disequilibrium with the functional polymorphism of ALDH2. We conducted Cox proportional hazards regression analysis considering potential risk factors collected from a baseline questionnaire. RESULTS: Over the median follow-up of 8 years, 121 cases of stroke were identified. Carrying the wild-type allele of the ALDH2 polymorphism increased stroke risk among men. The multivariate hazard ratio [95% confidence interval] of stroke was 2.02 [1.03-3.99] for the wild-type allele compared with the mutant alleles, but the association was attenuated after controlling for alcohol consumption. Combinations of the wild-type allele and other risk factors of stroke, such as old age, diabetes mellitus, and habitual snoring, synergistically increased the risk among men. Among women, however, the ALDH2 polymorphism was not associated with stroke risk. CONCLUSIONS: The prospective cohort study showed a significant association between a common ALDH2 polymorphism and stroke risk in Korean men, but not in Korean women, and also demonstrated that men with genetic disadvantages gain more risk when having risk factors of stroke. Thus, these men may need to make more concerted efforts to control modifiable risk factors of stroke.
Alcohol Drinking* ; Aldehyde Dehydrogenase* ; Alleles ; Cohort Studies* ; Diabetes Mellitus ; Female ; Follow-Up Studies ; Humans ; Linkage Disequilibrium ; Male ; Prospective Studies* ; Surveys and Questionnaires ; Risk Factors ; Snoring ; Stroke*

Background/aims: We investigated the effect of metabolic dysfunction-associated fatty liver disease (MAFLD) on future mortality and cardiovascular disease (CVD) using a prospective community-based cohort study. Methods: Individuals from two community-based cohorts who were 40 to 70 years old were prospectively followed for 16 years. MAFLD was defined as a high fatty liver index (FLI ≥60) plus one of the following conditions: overweight/obesity (body mass index ≥23 kg/m2), type 2 diabetes mellitus, or ≥2 metabolic risk abnormalities. Nonalcoholic fatty liver disease (NAFLD) was defined as FLI ≥60 without any secondary cause of hepatic steatosis. Results: Among 8,919 subjects (age 52.2±8.9 years, 47.7% of males), 1,509 (16.9%) had MAFLD. During the median follow-up of 15.7 years, MAFLD independently predicted overall mortality after adjustment for confounders (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.05 to 1.69) but NAFLD did not (HR, 1.20; 95% CI, 0.94 to 1.53). MAFLD also predicted CVD after adjustment for age, sex, and body mass index (HR, 1.35; 95% CI, 1.13 to 1.62), which lost its statistical significance by further adjustments. Stratified analysis indicated that metabolic dysfunction contributed to mortality (HR, 1.51; 95% CI, 1.21 to 1.89) and CVD (HR, 1.27; 95% CI, 1.02 to 1.59). Among metabolic dysfunctions used for defining MAFLD, type 2 diabetes mellitus in MAFLD increased the risk of both mortality (HR, 2.07; 95% CI, 1.52 to 2.81) and CVD (HR, 1.42; 95% CI, 1.09 to 1.85). Conclusions MAFLD independently increased overall mortality. Heterogeneity in mortality and CVD risk of subjects with MAFLD may be determined by the accompanying metabolic dysfunctions.

Background: Genome-wide association studies (GWAS) on type 2 diabetes mellitus (T2DM) have identified more than 400 distinct genetic loci associated with diabetes and nearly 120 loci for fasting plasma glucose (FPG) and fasting insulin level to date. However, genetic risk factors for the longitudinal deterioration of FPG have not been thoroughly evaluated. We aimed to identify genetic variants associated with longitudinal change of FPG over time. Methods: We used two prospective cohorts in Korean population, which included a total of 10,528 individuals without T2DM. GWAS of repeated measure of FPG using linear mixed model was performed to investigate the interaction of genetic variants and time, and meta-analysis was conducted. Genome-wide complex trait analysis was used for heritability calculation. In addition, expression quantitative trait loci (eQTL) analysis was performed using the Genotype-Tissue Expression project. Results: A small portion (4%) of the genome-wide single nucleotide polymorphism (SNP) interaction with time explained the total phenotypic variance of longitudinal change in FPG. A total of four known genetic variants of FPG were associated with repeated measure of FPG levels. One SNP (rs11187850) showed a genome-wide significant association for genetic interaction with time. The variant is an eQTL for NOC3 like DNA replication regulator (NOC3L) gene in pancreas and adipose tissue. Furthermore, NOC3L is also differentially expressed in pancreatic β-cells between subjects with or without T2DM. However, this variant was not associated with increased risk of T2DM nor elevated FPG level. Conclusion We identified rs11187850, which is an eQTL of NOC3L, to be associated with longitudinal change of FPG in Korean population.

Hypertension is the most prevalent disease worldwide and is itself a risk factor for cerebral, cardiac, and renal diseases. The inconsistency of candidate genes suggested by previous genomewide association studies (GWASs) may be due to not only differences in study design and genetic or environmental background but also the difference in the power of analysis between continuous traits and discrete traits. We analyzed 352,228 single nucleotide polymorphisms (SNPs) in 8842 unrelated Koreans obtained from Ansan and Ansung cohorts. We performed a series of GWA analyses using three different phenotype models; young hypertensive cases (278 subjects) versus elderly normotensive controls (680 subjects); the upper 25% (2211 hypertensive cases) versus the lower 25% of the SBP distribution (2211 hypotensive controls); and finally SBP and DBP as continuous traits (8842 subjects). The numbers of young hypertensive cases and elderly normotensive controls were not large enough to achieve genomewide significance. The model comparing the upper 25% subjects to the lower 25% of subjects showed a power that was approximate to that of QTL analysis. Two neighboring SNPs of the ATP2B1 gene, rs17249754 (SBP, p=2.53-10; DBP, p=1.28x10-8) and rs7136259 (SBP, p=1.30x10-9; DBP, p=6.41x10-8), were associated with both SBP and DBP. Interestingly, a SNP of the RPL6 gene, rs11066280, revealed a significant genomewide association with SBP in men only (p=3.85x10-8), and four SNPs located near the MAN2A1 gene showed a strong association with DBP only in elderly men aged 60-70 years (e.g., rs6421827, p=4.86x10-8). However, we did not observe any gene variant attaining genome-wide significance consistently in the three phenotype models except for the ATP2B1 gene variants. In general, the association signal with blood pressure was stronger in women than in men. Genes identified in GWASs are expected to open the way for prevention, early diagnosis, and personalized treatment of hypertension.
Aged ; Blood Pressure ; Case-Control Studies ; Cohort Studies ; Early Diagnosis ; Female ; Humans ; Hypertension ; Male ; Phenotype ; Polymorphism, Single Nucleotide ; Risk Factors

The aim of this study was to investigate the association between macronutrient composition and metabolic syndrome (MetS) incidence in Korean adults. Data were obtained from a cohort of 10,030 members aged 40 to 69 years who were enrolled from the 2 cities (Ansung and Ansan) between 2001 and 2002 to participate in the Korean Genome Epidemiology Study. Of these members, 5,565 participants, who were free of MetS and reported no diagnosis of cardiovascular disease at baseline, were included in this study. MetS was defined using the criteria of the National Cholesterol Education Program-Adult Treatment Panel III and Asia-Pacific criteria for waist circumference. MetS incidence rate were identified during a 2-year follow-up period. Baseline dietary information was obtained using a semi-quantitative food frequency questionnaire. Multivariate logistic regression analysis was used to evaluate the association between the quartiles of percentages of total calorie from macronutrients consumed and MetS incidence. In analyses, baseline information, including age, sex, body mass index, income status, educational status, smoking status, alcohol drinking status, and physical activity level was considered as confounding variables. Participants with the second quartile of the percentages of carbohydrate calorie (67%–70%) had a 23% reduced odds ratio (95% confidence interval, 0.61–0.97) for MetS incidence compared with those with the fourth quartile after adjusting for confounding variables. The findings suggest that middle aged or elderly Korean adults who consume approximately 67%–70% of calorie from carbohydrate have a reduced risk of MetS.
Adult* ; Aged ; Alcohol Drinking ; Body Mass Index ; Cardiovascular Diseases ; Cholesterol ; Cohort Studies ; Confounding Factors (Epidemiology) ; Diagnosis ; Education ; Educational Status ; Epidemiology ; Follow-Up Studies ; Genome ; Humans ; Incidence* ; Logistic Models ; Middle Aged ; Motor Activity ; Odds Ratio ; Smoke ; Smoking ; Waist Circumference