Differential Gene Expression in the Hippocampi of Nonhuman Primates Chronically Exposed to Methamphetamine, Cocaine, or Heroin

Objective@#Methamphetamine (MA), cocaine, and heroin cause severe public health problems as well as impairments in neural plasticity and cognitive function in the hippocampus. This study aimed to identify the genes differentially expressed in the hippocampi of cynomolgus monkeys in response to these drugs. @*Methods@#After the monkeys were chronically exposed to MA, cocaine, and heroin, we performed large-scale gene expression profiling of the hippocampus using RNA-Seq technology and functional annotation of genes differentially expressed. Some genes selected from RNA-Seq analysis data were validated with reverse transcription-quantitative polymerase chain reaction (RT-qPCR). And the expression changes of ADAM10 protein were assessed using immunohistochemistry. @*Results@#The changes in genes related to axonal guidance (PTPRP and KAL1), the cell cycle (TLK2), and the regulation of potassium ions (DPP10) in the drug-treated groups compared to the control group were confirmed using RT-qPCR. Comparative analysis of all groups showed that among genes related to synaptic long-term potentiation, CREBBP and GRIN3A were downregulated in both the MA- and heroin-treated groups compared to the control group. In particular, the mRNA and protein expression levels of ADAM10 were decreased in the MA-treated group but increased in the cocaine-treated group compared to the control group. @*Conclusion@#These results provide insights into the genes that are upregulated and downregulated in the hippocampus by the chronic administration of MA, cocaine, or heroin and basic information for developing novel drugs for the treatment of hippocampal impairments caused by drug abuse.

Composite follicular lymphoma and classic Hodgkin lymphoma

Composite lymphoma is very rare and a combination of Hodgkin lymphoma and non-Hodgkin lymphoma and even histiocytic tumors can occur. Because of the unfamiliarity, not only can this cause diagnostic problems, but can also affect treatment plan. We report a case of composite lymphoma in a 40-year-old male. Initial biopsy showed a composite lymphoma of follicular lymphoma grade 1 and classic Hodgkin lymphoma. After chemotherapy, another lymph node was taken because of disease progression, which revealed follicular lymphoma, grade 3a without Hodgkin lymphoma component.

Sudden Cardiac Death Caused by a Septic Coronary Artery Embolism as the First Clinical Presentation of Infective Endocarditis / 대한법의학회지

This report describes an uncommon and fatal case of myocardial infarction due to coronary embolus arising from vegetation in the aortic valve with a background of infective endocarditis (IE). There are various causes of fatal IE. Myocardial infarction due to septic emboli is rare. We report a case of sudden death in a 69-year-old woman with hyperlipidemia and no known cardiac disease. She had severe general weakness and was hospitalized for colonoscopy. The patient unexpectedly presented with cardiac arrest and died. The autopsy showed total occlusion of the left anterior descending artery by an embolus, which originated from the septic vegetation of the aortic valve. Myocardial infarction from septic emboli associated with IE can be fatal and manifested as the first presentation. In autopsy practice of deceased patients with IE, careful examination of the coronary arteries is required.

Clinicopathologic characteristics of HER2-positive pure mucinous carcinoma of the breast

Background@#Pure mucinous carcinoma (PMC) is a rare type of breast cancer, estimated to represent 2% of invasive breast cancer. PMC is typically positive for estrogen receptors (ER) and progesterone receptors (PR) and negative for human epidermal growth factor receptor 2 (HER2). The clinicopathologic characteristics of HER2-positive PMC have not been investigated. @*Methods@#Pathology archives were searched for PMC diagnosed from January 1999 to April 2018. Clinicopathologic data and microscopic findings were reviewed and compared between HER2-positive PMC and HER2-negative PMC. We also analyzed the differences in disease-free survival (DFS) and overall survival according to clinicopathologic parameters including HER2 status in overall PMC cases. @*Results@#There were 21 HER2-positive cases (4.8%) in 438 PMCs. The average tumor size of HER2-positive PMC was 32.21 mm (± 26.55). Lymph node metastasis was present in seven cases. Compared to HER2-negative PMC, HER2-positive PMC presented with a more advanced T category (p < .001), more frequent lymph node metastasis (p = .009), and a higher nuclear and histologic grade (p < .001). Microscopically, signet ring cells were frequently observed in HER2-positive PMC (p < .001), whereas a micropapillary pattern was more frequent in HER2-negative PMC (p = .012). HER2-positive PMC was more frequently negative for ER (33.3% vs. 1.2%) and PR (28.6% vs. 7.2%) than HER2-negative PMC and showed a high Ki-67 labeling index. During follow-up, distant metastasis and recurrence developed in three HER2-positive PMC patients. Multivariate analysis revealed that only HER2-positivity and lymph node status were significantly associated with DFS. @*Conclusions@#Our results suggest that HER2-positive PMC is a more aggressive subgroup of PMC. HER2 positivity should be considered for adequate management of PMC.

Age-related Effects of Heroin on Gene Expression in the Hippocampus and Striatum of Cynomolgus Monkeys

Objective@#The aim of this study was to investigate differentially expressed genes and their functions in the hippocampus and striatum after heroin administration in cynomolgus macaques of different ages. @*Methods@#Cynomolgus monkeys were divided by age as follows: 1 year (A1, n = 2); 3 to 4 years (A2, n = 2); 6 to 8 years (A3, n = 2); and older than 11 years (A4, n = 2). After heroin was injected intramuscularly into the monkeys (0.6 mg/kg), we performed large-scale transcriptome profiling in the hippocampus (H) and striatum (S) using RNA sequencing technology. Some genes were validated with real-time quantitative PCR. @*Results@#In the hippocampus, the gene expression of A1H was similar to that of A4H, while the gene expression of A2H was similar to that of A3H. Genes associated with the mitogen-activated protein kinase signaling pathway (STMN1, FGF14, and MAPT) and -aminobutyric acid-ergic synapses (GABBR2 and GAD1) were differentially expressed among control and heroin-treated animals. Differential gene expression between A1S and A4S was the least significant, while differential gene expression between A3S and A2S was the most significant. Genes associated with the neurotrophin signaling pathway (NTRK1 and NGFR), autophagy (ATG5), and dopaminergic synapses (AKT1) in the striatum were differentially expressed among control and heroin-treated animals. @*Conclusion@#These results suggest that even a single heroin exposure can cause differential gene expression in the hippocampus and striatum of nonhuman primates at different ages.

Elucidating the relationship of gingivitis and dental calculus with the periodontal health of 12-year-old children / 대한구강보건학회지

OBJECTIVES: This study aimed to investigate factors related to the periodontal health of 12-year-old children.METHODS: In 2015, the Korean Children's Oral Health Survey from the Ministry of Health & Social Welfare conducted a nationwide representative sample comprised of 23,702 12-year-old children. The calibration-trained dentists examined the gingivitis and dental calculus of the children taking into consideration of the Löe and Silness gingival index to diagnose gingivitis with a modified gingivitis scale. We used questionnaires to collect data from the children on dental treatments, the experience of dental pain and gingival bleeding, self-perceived oral health, and oral health behaviors. Data were analyzed using a complex samples Chi-square test, general linear model, and logistic regression. Significance was determined at P < 0.05.RESULTS: The prevalence of gingivitis was higher among males (OR 1.57), among children with poor perception (OR 1.19), dental calculus (OR 3.68), or gingival bleeding experience (OR 2.00), and among children not using dental floss (OR 1.69) or tongue cleaner (OR 1.90). The prevalence of dental calculus was higher among children with gingivitis (OR 3.82) and among children who had not visited a dental clinic in the preceding year (OR 1.31). However, dental calculus was lower among children with a higher frequency of daily toothbrushing (OR 0.75), intake of cariogenic foods (OR 0.90), or a higher DMFT index (OR 0.91).CONCLUSIONS: Children with dental calculus and gingival bleeding who did not visit a dental clinic in the preceding year also had a higher prevalence of gingivitis and dental calculus. The prevalence of children's dental calculus was lower among children with a high frequency of daily toothbrushing.

Caries reduction effect of permanent teeth from community water fluoridation program for 17 years in Jinju city / 대한구강보건학회지

OBJECTIVES: The community water fluoridation program was implemented in 1998 in Jinju city. The aim of the present study was to evaluate the effect of this 17-year community water fluoridation program on caries reduction in permanent teeth. METHODS: Evaluation surveys were conducted in 2015 on subjects aged 8, 10, 12, and 15 years in Jinju city. The examined dental data were compared with that of subjects of the same age groups living in the medium-sized cities from the 6th Korea National Health and Nutrition Examination Survey (KNHANES) (2013–2015). The total number of subjects was 1,026 in Jinju city and 453 in the control group. The odds ratio of caries experience rate and untreated tooth rate on permanent teeth in Jinju city compared to control group was estimated based on the differences in DMF and untreated teeth rates after adjusting for gender, age, and mean number of fissure-sealed teeth. The effect of community water fluoridation program on caries reduction in permanent teeth was estimated by the differences in adjusted DMFT scores between the program and control groups. RESULTS: The odds ratio of caries experience rate and untreated tooth rate on permanent teeth in Jinju city compared to control group was estimated as 0.501 and 0.178, respectively. The effect of community water fluoridation program on caries reduction in permanent teeth was estimated as 40.0%. CONCLUSIONS: These results suggested that the effect of community water fluoridation program on caries reduction in permanent teeth in Jinju city was so high that similar programs should be developed in other regions in Korea.

Evaluation of the Potential of Commercial Vitamin Drinks to Induce Tooth Erosion / 치위생과학회지

BACKGROUND: The market for vitamin drinks is expanding both in Korea and worldwide. However, it was difficult to find studies regarding the possibility of tooth erosion induction due to vitamin drinks. The purpose of the present in vitro study was to evaluate the effect of tooth erosion caused by a few commercial vitamin beverages on bovine teeth enamel in terms of erosion depth and fluorescence loss. METHODS: Three experimental groups (vitamin drinks), a positive control group (Coca-Cola), and a negative control group (mineral water) were established. Each group consisted of 5 specimens obtained from sound bovine teeth. The pH and titratable acidity of beverages were measured. Specimens were immersed in the beverages and artificial saliva for 6 and 18 hours, respectively. This cycle was repeated for 5 days. The depth of the tooth loss caused by tooth erosion (erosion depth) and maximum loss of fluorescence (Max ΔF) were measured using the microscope and quantified light-induced fluorescence-digital, respectively. For the statistical analysis, the Kruskal-Wallis test and ANOVA were used to compare the erosion depth and Max ΔF of the enamel surfaces. In addition, Spearman correlations were estimated. RESULTS: The pH of the three vitamin beverages ranged from 2.65 to 3.01, which is similar to that of the positive control group. All beverages, except mineral water, had sugar and acidic ingredients. Vitamin drinks and the positive control, Coca-Cola, caused tooth erosion lesions, and showed significant differences in erosion depth compared to mineral water (p<0.05). The vitamin beverages with low pH were associated with high erosion depth and Max ΔF. CONCLUSION: Vitamin drinks have the potential to cause tooth erosion.

Periodontal health status of adolescents aged 15 years in Jinju city / 대한구강보건학회지

OBJECTIVES: The purpose of this study was to evaluate the periodontal status of adolescents aged 15 years in Jinju city. METHODS: The study subjects were 506 adolescents aged 15 years in Jinju city. We investigated the prevalence and severity of periodontal disease using the Community Periodontal Index (CPI) recommended by the WHO. Data on the frequency of daily tooth-brushing were collected through self-reported questionnaires. The information obtained on both the periodontal health status and frequency of daily toothbrushing of adolescents in Jinju city was compared with the data from the 6th Korea National Health and Nutrition Examination Survey 2013-2015 (KNHANES-VI). The software utilized in the analysis was SPSS version 23. Statistical significance was set at P < 0.05. RESULTS: The rate of healthy periodontal status in Jinju city was lower compared to KNHANES-VI (57.7% versus 63.7%). The rate of gingival bleeding in Jinju city and KNHANES-VI was 11.3% and 10.8%, respectively. The rate of calculus in Jinju city and KNHANES-VI was 31.0% and 25.6%, respectively. The rates of gingival bleeding and calculus were not significantly different between Jinju city and KNHANES-VI. The healthy periodontal segments in Jinju city were more than those in KNHANES-VI (5.43 versus 5.25). The bleeding periodontal segments in Jinju city were less than those in KNHANES-VI (0.25 versus 0.45). However, the periodontal segments with calculus in Jinju city were not significantly different from those of KNHANES-VI (0.31 versus 0.30). The frequency of daily tooth-brushing in Jinju city was more than that in KNHANES-VI (2.67 versus 2.47). CONCLUSIONS: These findings suggest that appropriate oral health education should be widely conducted to promote periodontal health in adolescents.

Death Related to Nitrous Oxide Abuse: Two Cases Report / 대한법의학회지

Nitrous oxide is medically used as an anesthetic gas and as an additive in whipped cream production. Few cases of death from nitrous oxide intoxication have been reported in Korea. However, fatalities due to inhalation of pure nitrous oxide in an amount enough to cause death have been recently increasing. We report two cases of death related to nitrous oxide abuse with a review of literature focusing on the fact that nitrous oxide abuse can be considered as a possible cause of death if appliances with nitrous oxide contents were found during the investigation, and the autopsy and toxicological findings cannot be attributed to nitrous oxide intoxication.

The Effect of Probiotics, Antibiotics, and Antipyretic Analgesics on Gut Microbiota Modification

Human gut microbial community is playing a critical role in human health and associated with different human disease. In parallel, probiotics, antibiotics, and antipyretic analgesics (AAs) were developed to improve human health or cure human diseases. We therefore examined how probiotics, antibiotics, and AAs influence to the gut microbiota. Three independent case/control studies were designed from the cross-sectional cohort data of 1,463 healthy Koreans. The composition of the gut microbiota in each case and control group was determined via 16S ribosomal RNA Illumina next-generation sequencing. The correlation between microbial taxa and the consumption of each drug was tested using zero-inflated Gaussian mixture models, with covariate adjustment of age, sex, and body mass index (BMI). Probiotics, antibiotics, and AAs consumption yielded the significant differences in the gut microbiota, represented the lower abundance of Megasphaera in probiotics, the higher abundance of Fusobacteria in antibiotics, and the higher abundance of Butyrivibrio and Verrucomicrobia in AAs, compared to each control group. The reduction of Erysipelotrichaceae family was common in three drugs consumption.

The growth inhibitory effect of some vegetable oils on Streptococcus mutans and Lactobacillus casei / 대한구강보건학회지

OBJECTIVES: The purpose of this study was to evaluate the growth inhibitory effects of some vegetable oils on Streptococcus mutans (S. mutans) and Lactobacillus casei (L. casei). METHODS: Two bacterial strains and 5 kinds of test solutions (3 experimental groups: orange essential oil, olive oil, soybean oil; 1 positive control group: chlorhexidine solution; 1 negative control group: broth medium) were used in this study. S. mutans and L. casei pellets were exposed to 1 ml of one of the test solutions for 1 minute. Then, the treated bacterial cells were incubated in fresh broth medium for 0, 4, 8, 16, and 24 hours. The optical density of the broth medium was measured using an ELISA reader at 620 nm. A nonparametric Kruskal-Wallis test (with Mann-Whitney U tests) was performed to compare the change in optical density between different groups at different time points. RESULTS: Bacterial growth was significantly inhibited in all experimental groups compared to the negative control group. The growth of L. casei was less affected by experimental oils than that of S. mutans. Orange essential oil had the maximum growth inhibitory effect on S. mutans up to 8 hours, similar to that in the positive control group (P<0.01). Experimental oils had greater growth inhibitory effect on L. casei than chlorhexidine solution. CONCLUSIONS: This in vitro study confirmed the growth inhibitory effect of some vegetable oils on S. mutans and L. casei. Rising of the mouth using these vegetable oils is expected to have an anti-plaque effect, but additional clinical studies are needed to confirm this.

Association of the number of existing permanent teeth with the intake of macronutrients and macrominerals in adults aged 55-84 years based on the 5th KNHNES (2010-2012) / 대한구강보건학회지

OBJECTIVES: The aim of this study was to analyze the association between energy sources, fiber and mineral intake, and the number of existing permanent teeth in adults aged 55-84 years from the 5th Korea National Health and Nutrition Examination Survey (KNHNES) (2010-2012). METHODS: The subjects included 6,763 people who received oral examinations and answered questions on household income, smoking status and diet. We estimated the number of existing permanent teeth and food intake according to age group, sex, household income, and smoking status. A complex samples general linear model was applied to analyze the effect of nutrient intake on the number of existing permanent teeth adjusted for sex, household income, smoking status, and food intake. We calculated the mean intake of nutrients related to the number of existing permanent teeth in each tooth group. RESULTS: The reduction in the number of existing permanent teeth correlated with an increased carbohydrate intake and a decreased potassium intake. The carbohydrate intake was lower in subjects with 25 or more teeth than that in subjects with 9 or less teeth. Potassium intake was higher in subjects with 20 or more teeth. CONCLUSIONS: The number of existing permanent teeth showed a negative correlation with carbohydrate intake and a positive correlation with potassium intake. We should reduce carbohydrate intake and increased potassium intake from fruits and vegetables to prevent systemic disease caused by tooth loss.

False Increase in Whole Blood Tacrolimus Levels due to Interference in an Antibody-Conjugated Magnetic Immunoassay Method

Tacrolimus is an immunosuppressive agent used to prevent post-transplantation rejection. Tacrolimus has a narrow therapeutic window and therefore, its whole blood concentration is measured for therapeutic drug monitoring. In this report, we present two cases of falsely elevated tacrolimus concentrations identified in recipients of solid organ transplants due to analytical interferences in the antibody-conjugated magnetic immunoassay (ACMIA) method used. Tacrolimus concentrations measured using ACMIA were 4- to 8-fold higher than the values obtained using liquid-chromatography-tandem mass spectrometry (LC-MS/MS) or chemiluminescent micro-particle immunoassay. The cause of this interference remains unknown, but the identification of a possible false elevation of tacrolimus is of paramount importance in clinical practice. Pre-treatment of samples by ethanol extraction or using alternative methods of tacrolimus measurement such as LC-MS/MS are necessary to obtain reliable results in the event of an analytical interference.

In vitro quantification of occlusal caries lesion using QLF-D, ICDAS, and DIAGNOdent / 대한구강보건학회지

OBJECTIVES: To compare the QLF-D method and the ICDAS and DIAGNOdent techniques for in vitro quantification of occlusal caries and to assess the histological features of the caries. METHODS: One hundred and twenty-two extracted permanent teeth were selected, and the site of interest on the occlusal surface was examined using each detection method. The occlusal sites were classified according to the ICDAS II criteria based on the decision taken by two investigators, who have taken the ICDAS E-learning course. The examined site was then measured using the DIAGNOdent, and the peak value was recorded. In addition, by using the QLF-D, the occlusal site was photographed to obtain the DeltaFmax value. After all assessments were performed, the occlusal sites were vertically sectioned in order to assess the histological features. This was considered the gold standard. The histological criteria were graded using a 4-point scale as follows: S=sound (n=21), E1=limited enamel caries (n=27), E2=caries extending to the dento-enamel junction (n=49), D=caries involving the dentine (n=25). RESULTS: An ICDAS code between 0 and 4 was assigned to all the occlusal sites, and this revealed the QLF-D value, which was between -95 to 0. The DIAGNOdent value was between 8 and 99. The correlation values of QLF-D, ICDAS, and DIAGNOdent with the histological features were 0.68, 0.58, and 0.46, respectively (P<0.01). A highly significant correlation was observed between QLF-D and the gold standard, which showed a moderate correlation and an acceptable correlation was observed with ICDAS (r=0.75, P<0.01). A statistically significant difference was observed in the average QLF-D values of each histological grade i.e., -28.5 (S), -53.7 (E1), -68.1 (E2), and -84.4 (D). CONCLUSIONS: The QLF-D showed a significant correlation with the ICDAS and histological features. Therefore, visual inspection with QLF-D would improve the detection accuracy and ensure early diagnosis of dental caries.

Cost-benefit analysis of a water fluoridation program for 11 years in Jinju, Korea / 대한구강보건학회지

OBJECTIVES: The aim of this study was to estimate the economic costs and benefits of a water fluoridation program in the city of Jinju, Korea. METHODS: In 2009, dental surveys were conducted on 2,315 children aged 6-12 years in Jinju, which had been fluoridated for 11 years. The decayed/missing/filled teeth (DMFT) scores of children in Jinju were compared to the DMFT scores of same-aged children in non-fluoridated small- and medium-sized cities in the fourth Korean National Health and Nutrition Examination Survey conducted from 2007 to 2009 by the Korea Centers for Disease Control and Prevention. The reduced number of decayed permanent teeth by the water fluoridation program was estimated as the difference between the DMFT scores of children in Jinju and those in non-fluoridated small- and medium-sized cities. The economic benefits were estimated by the savings from reduced dental treatment costs by using the reduced number of decayed permanent teeth from the water fluoridation program. All annual costs and benefits were calculated from 1998 to 2009. The social rate and untreated rate of decayed teeth were applied as 3% and 20%, respectively. The annual benefit-cost ratio was estimated by using the annual benefits and cumulative program costs. RESULTS: The economic benefit in 2009 from a water fluoridation program was estimated as 57,496,000,000 Korean Won (KRW), and the cumulative cost in 2009 was estimated as 1,387,000,000 KRW. The net present value in 2009 from a water fluoridation program was 56,109,000,000 KRW. The benefit-cost ratio in 2009 was estimated as 41.4. CONCLUSIONS: The economic benefit of a water fluoridation program in Jinju city was evaluated as excellent.

Evaluation of release of fluoride from dental varnishes marketed in Korea / 대한구강보건학회지

OBJECTIVES: The purpose of this study was to compare the amount and rate of cumulative fluoride released over a period of 4 h from several varnishes marketed in Korea. METHODS: The following six commercial products were studied: cavity shield (CS, 22,600 ppm F), V varnish (VV, 22,600 ppm F), enamel pro varnish (EP, 22,600 ppm F), MI varnish (MI, 22600 ppm F), fluorine care (FC, 22600 ppm F), and fluor protector N (FP, 7700 ppm F). Five samples were collected from each varnish. Further, 10 mg of each varnish were applied onto an acrylic surface (diameter, 5 mm) and then immersed in 20 mL of distilled water at 37degrees C. The fluoride concentration in each sample was then analyzed after 30 min, 1, 2, 3, and 4 h, and after 4 days of exposure. RESULTS: The cumulative amount of fluoride released by FC (5.64+/-1.10 ppm) was significantly higher than that released by other products after 30 min. FC (8.55+/-1.85 ppm) and MI (8.21+/-0.81 ppm) released a significantly higher cumulative amount of fluoride after 4 h. The cumulative rate of fluoride released by FC (47.80+/-9.35%) was significantly higher than that of other products after 30 min. FC (72.44+/-15.68%) and MI (69.54+/-6.88%) showed a higher cumulative fluoride release rate after 4 h. MI sustainably released fluoride after 4 h and demonstrated a high fluoride release rate of 95.76%. CONCLUSIONS: The cumulative amount and rate of fluoride released by several varnishes were statistically significant at each time point. This data can be used by clinicians prior to selection of dental products.

Factors related to the experience of illegal dental treatments among Korean adults: The Fourth Korea National Health and Nutrition Examination Survey, 2007-2009 / 대한구강보건학회지

OBJECTIVES: The aim of the study was to analyze the factors related to the illegal dental treatment experience (IDTX) among Korean adults. METHODS: The raw data for the analysis of IDTX among Korean adults were obtained from the dataset of the Fourth Korea National Health and Nutrition Examination Survey conducted in 2007-2009. Stratified weighted subjects aged > or =45 years were selected according to region by using clustered sampling methods. In total, the data of 9,254 subjects, who participated in the interview and dental examinations related to the experience of illegal dental treatments, were analyzed using chi-square test, general linear model, and logistic regression analysis with complex sampling design by considering demographic and socioeconomic variables (age, gender, region, educational level, household income, and medical and dental delivery system) as well as oral status variables (prosthesis and number of natural remaining teeth). RESULTS: IDTX rate was 30% among adults aged > or =65 years. The age group with a high IDTX rate coincided with the age group with a high number of lost teeth. Most of the IDTX cases were presumed to be prosthetic treatments. The model comprising demographic, socioeconomic, and oral status variables had the highest explanation power. Significant variables were educational level, household income, prosthesis status, and number of remaining teeth. Women and persons under the medicaid system were more likely to undergo illegal dental treatments. CONCLUSIONS: Comprehensive prosthetic treatments are suggested to be included in the care services of the national health insurance and medicaid system to reduce the number of illegal dental treatments.

Pathway Analysis of Metabolic Syndrome Using a Genome-Wide Association Study of Korea Associated Resource (KARE) Cohorts

Metabolic syndrome (MetS) is a complex disorder related to insulin resistance, obesity, and inflammation. Genetic and environmental factors also contribute to the development of MetS, and through genome-wide association studies (GWASs), important susceptibility loci have been identified. However, GWASs focus more on individual single-nucleotide polymorphisms (SNPs), explaining only a small portion of genetic heritability. To overcome this limitation, pathway analyses are being applied to GWAS datasets. The aim of this study is to elucidate the biological pathways involved in the pathogenesis of MetS through pathway analysis. Cohort data from the Korea Associated Resource (KARE) was used for analysis, which include 8,842 individuals (age, 52.2 +/- 8.9 years; body mass index, 24.6 +/- 3.2 kg/m2). A total of 312,121 autosomal SNPs were obtained after quality control. Pathway analysis was conducted using Meta-analysis Gene-Set Enrichment of Variant Associations (MAGENTA) to discover the biological pathways associated with MetS. In the discovery phase, SNPs from chromosome 12, including rs11066280, rs2074356, and rs12229654, were associated with MetS (p < 5 x 10(-6)), and rs11066280 satisfied the Bonferroni-corrected cutoff (unadjusted p < 1.38 x 10(-7), Bonferroni-adjusted p < 0.05). Through pathway analysis, biological pathways, including electron carrier activity, signaling by platelet-derived growth factor (PDGF), the mitogen-activated protein kinase kinase kinase cascade, PDGF binding, peroxisome proliferator-activated receptor (PPAR) signaling, and DNA repair, were associated with MetS. Through pathway analysis of MetS, pathways related with PDGF, mitogen-activated protein kinase, and PPAR signaling, as well as nucleic acid binding, protein secretion, and DNA repair, were identified. Further studies will be needed to clarify the genetic pathogenesis leading to MetS.

Intracranial Extracerebral Glioneuronal Heterotopia with Adipose Tissue and a Glioependymal Cyst: A Case Report and Review of the Literature

No abstract available.