Genome-Wide Association Study on Longitudinal Change in Fasting Plasma Glucose in Korean Population

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.

Unveiling Genetic Variants Underlying Vitamin D Deficiency in Multiple Korean Cohorts by a Genome-Wide Association Study

Background@#Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS). @*Methods@#We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed. @*Results@#rs12803256, in the actin epsilon 1, pseudogene (ACTE1P) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B (PDE3B) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase (NADSYN1) and 7-dehydrocholesterol reductase (DHCR7), showed significantly different expression according to alleles. @*Conclusion@#The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, PDE3B, NADSYN1, and ACTE1P genes. The biological mechanism of a non-coding SNP (rs12803256) for DHCR7/NADSYN1 on vitamin D concentrations is unclear, warranting further investigations.

Clinical Significance of Body Fat Distribution in Coronary Artery Calcification Progression in Korean Population

Background@#Although obesity differs according to ethnicity, it is globally established as a solid risk factor for cardiovascular disease. However, it is not fully understood how obesity parameters affect the progression of coronary artery calcification (CAC) in Korean population. We sought to evaluate the association of obesity-related parameters including visceral adipose tissue (VAT) measurement and CAC progression. @*Methods@#This retrospective observational cohort study investigated 1,015 asymptomatic Korean subjects who underwent serial CAC scoring by computed tomography (CT) with at least 1-year interval and adipose tissue measurement using non-contrast CT at baseline for a routine checkup between 2003 and 2015. CAC progression, the main outcome, was defined as a difference of ≥2.5 between the square roots of the baseline and follow-up CAC scores using Agatston units. @*Results@#During follow-up (median 39 months), 37.5% of subjects showed CAC progression of a total population (56.4 years, 80.6% male). Body mass index (BMI) ≥25 kg/m2, increasing waist circumferences (WC), and higher VAT/subcutaneous adipose tissue (SAT) area ratio were independently associated with CAC progression. Particularly, predominance of VAT over SAT at ≥30% showed the strongest prediction for CAC progression (adjusted hazard ratio, 2.20; P<0.001) and remained of prognostic value regardless of BMI or WC status. Further, it provided improved risk stratification of CAC progression beyond known prognosticators. @*Conclusion@#Predominant VAT area on CT is the strongest predictor of CAC progression regardless of BMI or WC in apparently healthy Korean population. Assessment of body fat distribution may be helpful to identify subjects at higher risk.

Clinical Significance of Body Fat Distribution in Coronary Artery Calcification Progression in Korean Population

Background@#Although obesity differs according to ethnicity, it is globally established as a solid risk factor for cardiovascular disease. However, it is not fully understood how obesity parameters affect the progression of coronary artery calcification (CAC) in Korean population. We sought to evaluate the association of obesity-related parameters including visceral adipose tissue (VAT) measurement and CAC progression. @*Methods@#This retrospective observational cohort study investigated 1,015 asymptomatic Korean subjects who underwent serial CAC scoring by computed tomography (CT) with at least 1-year interval and adipose tissue measurement using non-contrast CT at baseline for a routine checkup between 2003 and 2015. CAC progression, the main outcome, was defined as a difference of ≥2.5 between the square roots of the baseline and follow-up CAC scores using Agatston units. @*Results@#During follow-up (median 39 months), 37.5% of subjects showed CAC progression of a total population (56.4 years, 80.6% male). Body mass index (BMI) ≥25 kg/m2, increasing waist circumferences (WC), and higher VAT/subcutaneous adipose tissue (SAT) area ratio were independently associated with CAC progression. Particularly, predominance of VAT over SAT at ≥30% showed the strongest prediction for CAC progression (adjusted hazard ratio, 2.20; P<0.001) and remained of prognostic value regardless of BMI or WC status. Further, it provided improved risk stratification of CAC progression beyond known prognosticators. @*Conclusion@#Predominant VAT area on CT is the strongest predictor of CAC progression regardless of BMI or WC in apparently healthy Korean population. Assessment of body fat distribution may be helpful to identify subjects at higher risk.

Identification of Novel Genetic Variants Related to Trabecular Bone Score in Community-Dwelling Older Adults

Background@#As the genetic variants of trabecular bone microarchitecture are not well-understood, we performed a genome-wide association study to identify genetic determinants of bone microarchitecture analyzed by trabecular bone score (TBS). @*Methods@#TBS-associated genes were discovered in the Ansung cohort (discovery cohort), a community-based rural cohort in Korea, and then validated in the Gene-Environment Interaction and Phenotype (GENIE) cohort (validation cohort), consisting of subjects who underwent health check-up programs. In the discovery cohort, 2,451 participants were investigated for 1.42 million genotyped and imputed markers. @*Results@#In the validation cohort, identified as significant variants were evaluated in 2,733 participants. An intronic variant in iroquois homeobox 3 (IRX3), rs1815994, was significantly associated with TBS in men (P=3.74E-05 in the discovery cohort, P=0.027 in the validation cohort). Another intronic variant in mitogen-activated protein kinase kinase 5 (MAP2K5), rs11630730, was significantly associated with TBS in women (P=3.05E-09 in the discovery cohort, P=0.041 in the validation cohort). Men with the rs1815994 variant and women with the rs11630730 variant had lower TBS and lumbar spine bone mineral density. The detrimental effects of the rs1815994 variant in men and rs11630730 variant in women were also identified in association analysis (β=–0.0281, β=–0.0465, respectively). @*Conclusion@#In this study, the rs1815994 near IRX3 in men and rs11630730 near MAP2K5 in women were associated with deterioration of the bone microarchitecture. It is the first study to determine the association of genetic variants with TBS. Further studies are needed to confirm our findings and identify additional variants contributing to the trabecular bone microarchitecture.

Identification of Novel Genetic Variants Related to Trabecular Bone Score in Community-Dwelling Older Adults

Background@#As the genetic variants of trabecular bone microarchitecture are not well-understood, we performed a genome-wide association study to identify genetic determinants of bone microarchitecture analyzed by trabecular bone score (TBS). @*Methods@#TBS-associated genes were discovered in the Ansung cohort (discovery cohort), a community-based rural cohort in Korea, and then validated in the Gene-Environment Interaction and Phenotype (GENIE) cohort (validation cohort), consisting of subjects who underwent health check-up programs. In the discovery cohort, 2,451 participants were investigated for 1.42 million genotyped and imputed markers. @*Results@#In the validation cohort, identified as significant variants were evaluated in 2,733 participants. An intronic variant in iroquois homeobox 3 (IRX3), rs1815994, was significantly associated with TBS in men (P=3.74E-05 in the discovery cohort, P=0.027 in the validation cohort). Another intronic variant in mitogen-activated protein kinase kinase 5 (MAP2K5), rs11630730, was significantly associated with TBS in women (P=3.05E-09 in the discovery cohort, P=0.041 in the validation cohort). Men with the rs1815994 variant and women with the rs11630730 variant had lower TBS and lumbar spine bone mineral density. The detrimental effects of the rs1815994 variant in men and rs11630730 variant in women were also identified in association analysis (β=–0.0281, β=–0.0465, respectively). @*Conclusion@#In this study, the rs1815994 near IRX3 in men and rs11630730 near MAP2K5 in women were associated with deterioration of the bone microarchitecture. It is the first study to determine the association of genetic variants with TBS. Further studies are needed to confirm our findings and identify additional variants contributing to the trabecular bone microarchitecture.

Hyperglycemia Is Associated with Impaired Muscle Quality in Older Men with Diabetes: The Korean Longitudinal Study on Health and Aging

BACKGROUND: The study aimed to investigate the influence of hyperglycemia on muscle quality in older men with type 2 diabetes. METHODS: This was a subsidiary study of the Korean Longitudinal Study of Health and Aging. Among 326 older men consenting to tests of body composition and muscle strength, 269 men were ultimately analyzed after the exclusion because of stroke (n=30) and uncertainty about the diagnosis of diabetes (n=27). Body composition was measured using dual-energy X-ray absorptiometry and computed tomography. Muscle strength for knee extension was measured using an isokinetic dynamometer. Muscle quality was assessed from the ratio of leg strength to the entire corresponding leg muscle mass. RESULTS: The muscle mass, strength, and quality in patients with type 2 diabetes did not differ significantly from controls. However, when patients with diabetes were subdivided according to their glycemic control status, patients with a glycosylated hemoglobin (HbA1c) level of ≥8.5% showed significantly decreased leg muscle quality by multivariate analysis (odds ratio, 4.510; P=0.045) after adjustment for age, body mass index, smoking amount, alcohol consumption, physical activity, and duration of diabetes. Physical performance status was also impaired in subjects with an HbA1c of ≥8.5%. CONCLUSION: Poor glycemic control in these older patients with diabetes was associated with significant risk of decreased muscle quality and performance status. Glycemic control with an HbA1c of <8.5% might be needed to reduce the risk of adverse skeletal and functional outcomes in this population.

Response: Hyperglycemia Is Associated with Impaired Muscle Quality in Older Men with Diabetes: The Korean Longitudinal Study on Health and Aging (Diabetes Metab J 2016;40:140-6)

No abstract available.

Sarcopenia and Obesity: Gender-Different Relationship with Functional Limitation in Older Persons

Age-related body composition changes such as sarcopenia and obesity affect functional decline in the elderly. We investigated the relationship between body composition parameters and functional limitation in older Korean adults. We enrolled 242 men and 231 women aged > or = 65 yr from the Korean elderly cohort. We used appendicular skeletal muscle mass (ASM) divided by height2 (ASM/Ht2) and ASM divided by weight (ASM/Wt). The isokinetic strength of knee extensor muscles were measured using an isokinetic device. Functional limitations were assessed using the Short Physical Performance Battery (SPPB) score less than nine. Men within the bottom tertile of ASM/Ht2 confer an increased risk for functional limitation compared with those within the top tertile (OR, 6.24; 95% CI, 1.78-22.0). However, in women, subjects within the lowest ASM/Wt tertile had a higher risk compared with those within the highest tertile instead of ASM/Ht2 (OR, 7.60; 95% CI, 2.25-25.7). Leg muscle strength remained the strong measure even after controlling for muscle mass only in women. Only large waist circumference was positively associated with functional limitation only in women. We might consider a different muscle index to assess functional limitation according to the gender.

Erratum: Correction of Figure. Sarcopenia and Obesity: Gender-Different Relationship with Functional Limitation in Older Persons

The legends of Fig. 1 were marked incorrectly.

Effect of Thyroid Hormone to the Expression of Bile Salt Export Pump

BACKGROUND: Bile acids were important for the regulation of cholesterol homeostasis. Thyroid hormone increased the expression of CYP7A1 (cholesterol 7alpha-hydroxylase), catalyzing the first step in the biosynthesis of bile acids. However, the effect of thyroid hormone on bile acid export has not been previously assessed. The principal objective of this study is to evaluate the effects of thyroid hormone on the bile salt export pump (BSEP). METHODS: Thyroid hormone, T3 (1 mg/g) was administered to male mice via intraperitoneal injection. After 6 hours and 5 days of T3 treatment, we measured serum total and LDL cholesterol and hepatobiliary bile acid concentrations. We assessed the changes associated with bile acid synthesis and transport. In order to evaluate the direct effect of thyroid hormone, we assessed the changes in the levels of BSEP protein after T3 administration in human hepatoma cells. RESULTS: Serum total and LDL cholesterol were reduced and hepatobiliary bile acid concentrations were increased following T3 treatment. Expressions of Cyp7a1 and BSEP mRNA were increased following T3 treatment. The levels of the BSEP protein in the mouse liver as well as in the human hepatoma cells were increased after T3 treatment. CONCLUSION: Thyroid hormone can regulate LDL cholesterol metabolism. It increases bile acid synthesis and the excretion of bile acids via increased BSEP expression.

The Predictors of Anger Expression of the Homeless in the Shelters

PURPOSE: The purposes of this study were to examine the level of anger, anger expression, depression, psychosomatic symptom and perceived health status, and to identify the influencing factors of anger expression in shelter residents. METHODS: This study employed a descriptive correlational design. Data were collected from 407 homeless people residing at 27 shelters using structured instruments. RESULTS: The level of anger expression was different by age, educational level, existence of children, and duration of shelter residency. Anger expression was significantly correlated with depression, psychosomatic symptoms and perceived health status. The predictors of high-level anger expression was younger age, low educational level, duration of shelter residency in Model 1 (F=6.884, p<.001, Adj. R2=.065), and depression and psychosomatic symptoms in Model 2 (F=7.197, p<.001, Adj. R2=.113). CONCLUSION: This study suggested that the homeless in the shelters had various psychological vulnerabilities, and therefore more individualized programs based on their needs and psychological health status should be provided for the homeless.

Structural Modeling of Parenting Behavior of Mothers with Preschool Children

PURPOSE: This study was done to build and test a theoretical model that could be used to explain and predict parenting behavior of mothers with preschool children. METHODS: The participants were 298 mothers with preschool children. Data were analyzed using the SAS (Statistical Analysis System) and AMOS (Analysis of Moment Structures) programs. RESULTS: Parenting stress showed a direct effect on parenting satisfaction. Parenting efficacy showed a direct effect on parenting behavior. Parenting stress showed an indirect effect on parenting behavior. Parenting efficacy was found to mediate the relationship between parenting stress and parenting behavior. Income and mother's perfectionism had an impact on parenting behavior. CONCLUSION: The outcomes of this study indicate the necessity of designing intervention programs that emphasize increasing parenting efficacy in order to increase positive parenting behavior.

Anger, Anger Expression, and Biopsychosocial Health in Korean Adolescents / 정신간호학회지

PURPOSE: The purpose of this study was to explore status and relationships of anger and its expression type to biopsychosocial health in Korean adolescents. METHODS: This cross-sectional study used four reliable survey questionnaires that measure anger, depression, resilience, and psychosomatic symptoms. Data were collected from 18,752 students of 36 middle schools and 23 high schools located in 23 administrative districts in Seoul, Korea. RESULTS: The Korean adolescents who completed the questionnaires indicated moderate level of trait anger. 45% of them demonstrated using one of three undesirable types of anger expression such as dysfunctional anger-in and anger-out, high level anger-in, or high level anger-out. Also, level of trait anger and types of anger expression were significantly associated with resilience, depression, and psychosomatic health status. CONCLUSION: School-based mental health education such as anger management programs for Korean adolescents might be necessary to help them develop desirable and effective coping skills and strategies.

Anger, Anger Expression, and Biopsychosocial Health in Korean Adolescents / 정신간호학회지

PURPOSE: The purpose of this study was to explore status and relationships of anger and its expression type to biopsychosocial health in Korean adolescents. METHODS: This cross-sectional study used four reliable survey questionnaires that measure anger, depression, resilience, and psychosomatic symptoms. Data were collected from 18,752 students of 36 middle schools and 23 high schools located in 23 administrative districts in Seoul, Korea. RESULTS: The Korean adolescents who completed the questionnaires indicated moderate level of trait anger. 45% of them demonstrated using one of three undesirable types of anger expression such as dysfunctional anger-in and anger-out, high level anger-in, or high level anger-out. Also, level of trait anger and types of anger expression were significantly associated with resilience, depression, and psychosomatic health status. CONCLUSION: School-based mental health education such as anger management programs for Korean adolescents might be necessary to help them develop desirable and effective coping skills and strategies.

Comparison of Cardiovascular Health Status and Health Behaviors in Korean Women based on Household Income

PURPOSE: In this study cardiovascular health status and health behavior of Korean women based on their household income were explored. METHODS: For this cross-sectional study, 91 women residing in the community were recruited to complete survey questionnaires and biophysical tests including blood pressure (BP), body mass index (BMI), body fat rate, waist circumference (WC), and blood chemistry tests. RESULTS: Compared to non-low income women (NLIW), low income women (LIW) were more likely to be older, less educated, and jobless, and further more LIW were postmenopause and reported having been diagnosed with hypertension or hypercholesterolemia. Significant differences were found in systolic BP, triglyceride level, BMI, body fat rate, and WC between the groups. Two fifths of the LIW had indications for metabolic syndrome. Their 10-yr risk estimate of myocardioal infarction or coronary death demonstrated a higher probability than that of NLIW. Although these significant differences were due to age gap between the groups, advanced age is known to be one of the key characteristics of LIW as well as a non-modifiable risk factor. CONCLUSION: Effective community programs for vulnerable women at risk of cardiovascular disease should be based on strategies targeting unhealthy behaviors and modifiable risk factors.

Investigation of Sarcopenia and Its Association with Cardiometabolic Risk Factors in Elderly Subjects

BACKGROUND: The aim of this study was to investigate sarcopenia and its association with cardiometabolic risk factors in a community-based elderly cohort in Korea. METHODS: We recruited 287 men and 278 women aged 65 years or older and without physical disability. Appendicular skeletal muscle mass (ASM) was measured with dual energy X-ray absorptiometry. We used two definitions for sarcopenia-ASM divided by height2 (kg/m2) or by weight (%) <1 SD below the sex-specific mean for young adults. We compared RBP-4, adiponectin, hsCRP, lipid profiles, and insulin resistance between the sarcopenic and normal groups using ASM/Ht2 and ASM/Wt. RESULTS: The prevalence of sarcopenia was 35.3% in men and 13.4% in women with sarcopenia defined by ASM/Ht2. However, it was 38.3% in men and 62.6% in women by ASM/Wt. In correlation analysis, body mass index was positively correlated with ASM/Ht2 and negatively correlated with ASM/Wt. The sarcopenic group, when defined as ASM/Ht2, showed lower RBP4, fasting plasma glucose, and HOMA-IR and higher adiponectin than the normal group but not significantly different lipid profiles. The sarcopenic group defined by ASM/Wt had higher RBP4, fasting plasma glucose, and HOMA-IR, and lower adiponectin than the normal group in both sexes. Only in the males did the sarcopenic group defined by ASM/Wt reveal higher total cholesterol, triglycerides, and LDL cholesterol, and lower HDL cholesterol than the normal group. CONCLUSION: In conclusion, the sarcopenic group defined by ASM/Wt was more closely associated with cardiometabolic risk factors than the normal group in a community-based elderly cohort.

Development and Evaluation of a School-based Anger Management Program (SAMP) for Adolescents

PURPOSE: This study was done to develop a school-based anger management program (SAMP) of 4 sessions and examine its effects on the anger, anger expression, psychosomatic responses, psychosocial responses, and immunologic responses in adolescents. METHODS: A quasi-experimental study using a nonequivalent control group, pre-post design with repeated measures was used. Chi-square test, t-test, paired t-test, and Fisher's exact test were used to analyze the data. RESULTS: There were no differences between the experimental and control groups in outcome variables except for lymphocytes. However, following additional analyses, statistically significant differences by time point were observed for pain sensitivity, T cell, Helper T (Th) cell, Suppressor (Ts) cell and Natural Killer (NK) cell post-treatment, entrapment and psychosomatic symptoms at the 4-week follow-up, and resilience at the 10-week follow-up for the experimental group. CONCLUSION: Although some modifications in contents and administration will be required to increase the effectiveness of the program for anger management, SAMP can be used to promote anger management ability in adolescents.

Parenting Stress and Related Factors of Employed and Non-employed Mothers with Preschool Children / 여성건강간호학회지

PURPOSE: This study was done to compare the level of parenting stress, entrapment, satisfaction of paternal support, and marital satisfaction between employed and non-employed mothers and to identify significant predictors for parenting stress. METHODS: With a cross-sectional, correlational study design, a sample of study was consisted of 175 women who were employed or non-employed with preschool children through convenience sampling. Data were collected with a structured self-administered questionnaire and analyzed by chi-square-test, t-test, Pearson's coefficients, and multiple regression analysis using SPSS program. RESULTS: Results shows that the level of parenting stress of nonemployed mothers was significant higher than that of employed mother. The parenting stress was negatively correlated to marital satisfaction and positively correlated to entrapment in both of them. Entrapment was significant predictors explaining parenting stress in both of them and level of maternal education and satisfaction of paternal support and was significant predictors explaining parenting stress of non-employed mothers. CONCLUSION: Entrapment was very important factors to management parenting stress of both employed and non-employed mothers. Especially, satisfaction of paternal support and marital satisfaction was very important factor to manage parenting stress of mothers.

Effects of a Breast Feeding Promotion Program for Working Women

PURPOSE: The purpose of this study was to measure the effects of a breast feeding promotion program for working women on breast feeding continuation, mother-infant attachment, and maternal sensitivity. METHODS: The design of this study is nonequivalent control group design with repeated measures. RESULTS: There were significant differences in breast feeding continuation between two groups at each time point except 2 days and 1 week after delivery. The scores of mother-infant attachment and maternal sensitivity of experimental group were higher than those of the control group, but there were no significant differences between two groups. CONCLUSION: Although some modifications in contents and administration will be required to increase the effectiveness of the program, breast feeding promotion program for working women can be an effective nursing intervention which can facilitate breast feeding continuation and mother-infant relationships.