Background: The heterogeneity of chronic kidney disease (CKD) and fragmented analysis methods hinder the precise identification of novel biomarkers. We addressed this challenge using two independent cohorts to integrate genomics and metabolomics, aiming to identify cause-specific biomarkers for CKD in the Korean population. Methods: A longitudinal genome-wide association study using the Cox proportional hazards model was conducted using the Ansan and Ansung cohort. To validate these genomic biomarkers and integrate them with plasma metabolomics biomarkers, we utilized a hospital-based biopsy cohort to identify cause-specific CKD biomarkers. Within the biopsy cohort, we analyzed four disease subsets, including type 2 diabetic kidney disease (DKD), hypertensive nephropathy (HN), immunoglobulin A nephropathy (IgAN), and membranous nephropathy (MN), and compared them with healthy individuals. Significant single nucleotide polymorphisms(SNPs) and metabolites for each CKD subset were identified through logistic regression and correlation-based network analyses. Subsequently, we analyzed the risk of disease progression associated with the identified pairs. Results: A total of 448 variants associated with CKD occurrence were identified, with significant differences in several genetic variants and metabolites observed among patients with DKD, HN, IgAN, and MN compared to healthy individuals. Among 36 SNP-metabolite pairs, those involing FOXB1 and ZFP42 were associated with DKD, whereas pairs involving MMRN1 and SYNJ2 were linked to MN. Notably, the rs1025170 variant in FOXB1 and tyrosine pair was correlated with DKD progression. Conclusion Integrating genomics and metabolomics across independent cohorts enables the discovery of cause-specific biomarkers for the occurrence and progression of CKD in the Korean population.

This study aimed to determine the association between trajectories of obesity status and prediabetes reversion to normoglycemia or progression to diabetes. The study included 14,452 participants from the National Health Insurance Service-National Health Screening (NHIS-HEALS) cohort who continuously had prediabetes glycemic status during the index period (2002-2008), definedby their fasting plasma glucose. The exposure of the study was the trajectories of obesity (defined by body mass index ≥ 25 kg/m 2 ) generated using latent class growth analysis. The outcomes were reversion to normoglycemia or progression to diabetes, whichever occurred first during the follow-up period (2009-2016). The association between trajectories and changes in prediabetes status were examined using cause-specific hazard regression by obtaining the hazard ratio (HR) with a 95% CI. We identified three distinct trajectories which were “Stable obese”, “Stable non-obese” and “Obese to non-obese”. After a median follow-up of 2years, 51.99% of participants had their glycemic status back to normoglycemia and 32.17% developed diabetes. Compared with participants in the “Stable obese” group, those in “Stable non-obese” and “Obese to non-obese” groups were more likely to have reversion to normoglycemia (HR with a 95% CI = 1.30 [1.23-1.37] and 1.15 [1.07-1.24], respectively) and lower risk of developingdiabetes (0.78 [0.73-0.84] and 0.90 [0.82-0.98], respectively). The findings suggest that maintaining or achieving a non-obese sta-tus is linked to higher reversion to normoglycemia as well as lower risks of developing diabetes.

OBJECTIVES: Lifestyles, including exercise behaviors, change continually over time. This study examined whether the clinical biomarkers (CBs) related to cardiometabolic diseases (CMDs) and their relationships differed with changes in exercise behavior. METHODS: The Ansan-Ansung cohort study (third to fifth phases; n=2,668) was used in the current study. Regular exercise behavior was investigated using a yeso questionnaire. Changes in exercise behavior were classified into 4 groups: Y-N, N-Y, Y-Y, and N-N, with “Y” indicating that a participant regularly engaged in exercise at a given time point and “N” indicating that he or she did not. Fourteen CBs related to CMDs were used, and the associations between changes in exercise behavior and relative changes in CBs were examined. CB networks were constructed and topological comparisons were conducted. RESULTS: Y-N was associated with increases in fasting blood sugar and insulin levels in men, and increased total cholesterol and low-density lipoprotein cholesterol levels in women. Meanwhile, N-Y was inversely associated with body fat percentage, visceral fat percentage, fasting insulin, and triglyceride level. Waist circumference played a central role in most networks. In men, more edges were found in the N-Y and Y-Y groups than in the N-N and Y-N groups, whereas women in the N-Y and Y-Y groups had more edges than those in the N-N and Y-N groups. CONCLUSIONS Consistent exercise or starting to engage in regular exercise had favorable effects on CBs related to CMDs, although their network patterns differed between the sexes.

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.

No abstract available.
Meningitis ; Pneumocephalus

PURPOSE: The high mobility group box 1 (HMGB1) protein has roles in apoptosis and immune responses by acting as a ligand for receptor for advanced glycation end products (RAGE), Toll-like receptors (TLRs), and triggering receptor expressed on myeloid cells 1. In particular, HMGB1/RAGE is involved in tumor metastasis by inducing matrix metalloproteinase 2 (MMP2) and MMP9 expression. We investigated the associations between genetic variations in HMGB1-related genes and disease-free survival (DFS) and overall survival (OS) in Korean female breast cancer patients. METHODS: A total of 2,027 patients in the Seoul Breast Cancer Study were included in the analysis. One hundred sixteen single nucleotide polymorphisms (SNPs) were extracted from eight genes. A multivariate Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence interval (CI) of each SNP. The effects of the SNPs on breast cancer prognosis were assessed at cumulative levels with polygenic risk scores. RESULTS: The SNPs significantly associated with DFS were rs243867 (hazard ratio, 1.26; 95% CI, 1.05–1.50) and rs243842 (hazard ratio, 1.24; 95% CI, 1.03–1.50); both SNPs were in MMP2. The SNPs significantly associated with OS were rs243842 in MMP2 (hazard ratio, 1.33; 95% CI 1.03–1.71), rs4145277 in HMGB1 (hazard ratio, 1.29; 95% CI, 1.00–1.66), rs7656411 in TLR2 (hazard ratio, 0.76; 95% CI, 0.60–0.98), and rs7045953 in TLR4 (hazard ratio, 0.50; 95% CI, 0.29–0.84). The polygenic risk score results for the DFS and OS patients showed third tertile hazard ratios of 1.72 (95% CI, 1.27–2.34) and 2.75 (95% CI, 1.79–4.23), respectively, over their first tertile references. CONCLUSION: The results of the present study indicate that genetic polymorphisms in HMGB1-related genes are related to breast cancer prognosis in Korean women.
Advanced Glycosylation End Product-Specific Receptor ; Apoptosis ; Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Female ; Genetic Predisposition to Disease* ; Genetic Variation ; HMGB1 Protein ; Humans ; Matrix Metalloproteinase 2 ; Myeloid Cells ; Neoplasm Metastasis ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Prognosis* ; Proportional Hazards Models ; Seoul ; Toll-Like Receptors

No abstract available.
Parkinsonian Disorders*

BACKGROUND: Quality-of-life measurement represents an important tool for evaluating the management and impact of headache on individuals and society. The Headache Impact Test-6 (HIT-6) is a simple instrument developed to assess headache-related disability in Western countries. The objective of this study was to determine the reliability and validity of the Korean HIT-6. METHODS: Participants were recruited from patients who visited the Neurology Clinic of Hallym University Sacred Heart Hospital due to headache. The survey included the SF-36 and HIT-6. Headache diagnosis was assigned using ICHD-II after completing a semistructured diagnostic interview. RESULTS: A total of 43 patients were recruited, who were aged 35.2+/-13.6 years (mean+/-SD). Thirty-three and three were diagnosed as having migraine and probable migraine, respectively. Eight and two were diagnosed with tension-type and probable tension-type headache, respectively. There was a negative correlation between the total SF-36 and HIT-6 scores (Spearman's correlation coefficient=-0.64, p<0.01). Similar significant negative correlations were also observed between SF-36 physical health summary and HIT-6 scores (Spearman's correlation coefficient=-0.54, p<0.01), and between SF-36 mental summary and HIT-6 scores (Spearman's correlation coefficient=-0.60, p<0.01). The Cronbach's alpha of HIT-6 was 0.85. CONCLUSIONS: The Korean HIT-6 is a valid and reliable instrument for assessing headache-related quality of life.
Aged ; Headache ; Heart ; Humans ; Migraine Disorders ; Neurology ; Quality of Life ; Reproducibility of Results ; Tension-Type Headache

BACKGROUND: Migraine can cause suffering and reduce functioning and productivity. Migraine is usually suboptimally treated, with many migraineurs not being satisfied with the applied acute treatment. Migraine-ACT is a four-item assessment tool used by clinicians to identify patients who require a change in their acute treatment. The objective of this study was to determine validity and reliability of the Korean Migraine-ACT. METHODS: Participants who visited Hallym University Sacred Heart Hospital neurology clinic for headache were recruited. The survey employed SF-36, HIT-6, and Migraine-ACT. Headache diagnosis was assigned on ICHD-II after completing a semistructured diagnostic interview. RESULTS: A total of 52 migraine patients aged 38.7+/-14.7 years (mean+/-SD) were recruited. There was a positive correlation between general summary scores on SF-36 and Migraine-ACT (Spearman's correlation coefficient=0.39, p<0.05) and a negative correlation between HIT-6 scores and Migraine-ACT scores (Spearman's correlation coefficient=.0.52, p<0.05). Cronbach's alpha of Migraine-ACT was 0.78. CONCLUSIONS: These results indicate that Korean Migraine-ACT is a valid and reliable instrument to identify migraine patients who require a change in their acute treatment.
Aged ; Efficiency ; Headache ; Heart ; Humans ; Migraine Disorders ; Neurology ; Reproducibility of Results ; Stress, Psychological

Myoclonus manifests in a variety of situations including epilepsy, metabolic derangements, brain lesions, and toxicity of drugs. A 57-year-old woman with end-stage renal disease was given gabapentin 900 mg/day for legs' paresthesia. Two days after taking gabapentin, multifocal myoclonus developed involving all extremities. Three days after discontinuation of gabapentin, myoclonus resolved completely. No deterioration of renal function was noted before and after the occurrence of myoclonus. Administration of gabapentin should be performed with caution in patients with impaired renal function.
Brain ; Epilepsy ; Extremities ; Female ; Humans ; Kidney Failure, Chronic* ; Middle Aged ; Myoclonus* ; Paresthesia