RESUMO
OBJECTIVE: The identification of allergic rhinitis (AR) in early life is important for the target of intervention. AR is caused by various environmental factors, including house dust mites. We investigated the relationship between the Dermatophagoides farinae (Der f)-IgE and eosinophil in mothers with AR at delivery and the eosinophil levels and AR incidence in children. METHODS: The study participants were 983 mother-child pairs from the COhort for Childhood Origin of Asthma and Allergic Diseases. AR was diagnosed by a doctor at delivery in mother and at 3 years of age in offspring. The association between eosinophil level and AR was assessed using logistic regression analysis. RESULTS: The Der f-IgE level in mother having AR at delivery was associated with the mother's eosinophil level, and the mother's eosinophil level was associated with the child's eosinophil level both at age 1 and 3. The risk of AR at age 3 in children was increased according to increased eosinophil levels in mothers at delivery and in children both aged 1 and 3 years (adjusted odds ratio [aOR] and 95% confidence interval [CI]: 2.57 [1.14-5.78], 2.28 [1.02-5.13], respectively). The risk of childhood AR at the age of 3 is increased when both mothers and children have high eosiniophils (aOR and 95% CI: 2.62 [1.01-6.79], 1.37 [0.98-1.91]). CONCLUSIONS: Der f-IgE in mothers at delivery was related to eosinophil levels in mothers with AR and higher level of eosinophils in both mother and children was associated with the increased risk of AR incidence at the first 3 years of life of children.
Assuntos
Asma , Rinite Alérgica , Feminino , Humanos , Lactente , Pré-Escolar , Eosinófilos , Incidência , Imunoglobulina E , Rinite Alérgica/epidemiologia , Asma/epidemiologia , Asma/etiologia , Asma/diagnósticoRESUMO
Excessive alcohol intake is an important cause of major public health problem in East Asian countries. Growing evidence suggests that genetic factors are associated with alcohol consumption and the risk for alcohol-associated disease, and these factors contribute to the risk of developing chronic diseases, including diabetes. This study aims to investigate the association of type 2 diabetes with genetic polymorphisms within HECTD4 based on alcohol exposure. We performed a genome-wide association study involving the cohorts of the KoGES-HEXA study (n = 50,028) and Ansan and Ansung study (n = 7,980), both of which are prospective cohort studies in Korea. The top three single-nucleotide polymorphisms (SNPs) of the HECTD4 gene, specifically rs77768175, rs2074356 and rs11066280, were found to be significantly associated with alcohol consumption. We found that individuals carrying the variant allele in these SNPs had lower fasting blood glucose, triglyceride, and GGT levels than those with the wild-type allele. Multiple logistic regression showed that statistically significant associations of HECTD4 gene polymorphisms with an increased risk of type 2 diabetes were found in drinkers. Namely, these SNPs were associated with decreased odds of diabetes in the presence of alcohol consumption. As a result of examining the effect of alcohol on the expression of the HECTD4 gene, ethanol increased the expression of HECTD4 in cells, but the level was decreased by NAC treatment. Similar results were obtained from liver samples of mice treated with alcohol. Moreover, a loss of HECTD4 resulted in reduced levels of CYP2E1 and lipogenic gene expression in ethanol-treated cells, while the level of ALDH2 expression increased, indicating a reduction in ethanol-induced hepatotoxicity.
Assuntos
Diabetes Mellitus Tipo 2 , Consumo de Bebidas Alcoólicas/efeitos adversos , Aldeído-Desidrogenase Mitocondrial/genética , Animais , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Etanol , Jejum , Estudo de Associação Genômica Ampla , Glucose , Humanos , Camundongos , Polimorfismo de Nucleotídeo Único , Prevalência , Estudos Prospectivos , Triglicerídeos , Ubiquitina-Proteína Ligases/genéticaRESUMO
The prevalence of obesity among children and adolescents with autism spectrum disorder (ASD) is higher than that among typically developing children and adolescents. However, very few studies have explored the genetic factors associated with obesity in children and adolescents with ASD. Thus, the aim of this study was to examine the associations between 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) gene polymorphisms and obesity among children and adolescents with ASD. The study participants consisted of 33 children and adolescents with ASD and 271 age- and sex-matched typically developing controls. We compared the metabolic traits (body mass index, blood pressure, triglyceride, high-density lipoprotein, and fasting glucose levels) between the ASD and control group. Furthermore, we assessed the genotypes of rs12654264 in the HMGCR gene within the participants with ASD, and compared metabolic traits among the different allele subgroups. The mean body mass index (BMI) and triglyceride level of the ASD group were significantly higher than those of the control group. Within the ASD group, the triglyceride level of participants with rs12654264-T alleles was significantly higher than that of participants with A-alleles. A pattern of increasing values in the BMI and fasting glucose was also observed in participants with T allele. This is the first study to show that obesity in children and adolescents with ASD is associated with the cholesterol synthesis pathway. Future studies are needed to further clarify the molecular mechanisms by which the HMGCR gene influences metabolic traits.
Assuntos
Transtorno do Espectro Autista , Hidroximetilglutaril-CoA Redutases , Metabolismo dos Lipídeos , Obesidade Infantil , Adolescente , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/metabolismo , Criança , Humanos , Hidroximetilglutaril-CoA Redutases/genética , Obesidade Infantil/genética , Polimorfismo Genético/genéticaRESUMO
We conducted a retrospective study of Middle East respiratory syndrome coronavirus (MERS-CoV) viral load kinetics using data from patients hospitalized with MERS-CoV infection between 19 May and 20 August 2015. Viral load trajectories were considered over the hospitalization period using 1714 viral load results measured in serial respiratory specimens of 185 patients. The viral load levels were significantly higher among nonsurvivors than among survivors (Pâ =â .003). Healthcare workers (Pâ =â .001) and nonspreaders (Pâ <â .001) had significantly lower viral loads. Viral RNA was present on the day of symptom onset and peaked 4-10 days after symptom onset.
Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Adulto , Idoso , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/transmissão , Surtos de Doenças , Transmissão de Doença Infecciosa , Feminino , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , RNA Viral/análise , República da Coreia/epidemiologia , Estudos Retrospectivos , Carga Viral , Eliminação de Partículas ViraisRESUMO
Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness and has a high mortality of â¼34%. However, since its discovery in 2012, an effective vaccine has not been developed for it. To develop a vaccine against multiple strains of MERS-CoV, we targeted spike glycoprotein (S) using prime-boost vaccination with DNA and insect cell-expressed recombinant proteins for the receptor-binding domain (RBD), S1, S2, SΔTM, or SΔER. Our S subunits were generated using an S sequence derived from the MERS-CoV EMC/2012 strain. We examined humoral and cellular immune responses of various combinations with DNA plasmids and recombinant proteins in mice. Mouse sera immunized with SΔER DNA priming/SΔTM protein boosting showed cross-neutralization against 15 variants of S-pseudovirions and the wild-type KOR/KNIH/002 strain. In addition, these immunizations provided full protection against the KOR/KNIH/002 strain challenge in human DPP4 knock-in mice. These findings suggest that vaccination with the S subunits derived from one viral strain can provide cross-protection against variant MERS-CoV strains with mutations in S. DNA priming/protein boosting increased gamma interferon production, while protein-alone immunization did not. The RBD subunit alone was insufficient to induce neutralizing antibodies, suggesting the importance of structural conformation. In conclusion, heterologous DNA priming with protein boosting is an effective way to induce both neutralizing antibodies and cell-mediated immune responses for MERS-CoV vaccine development. This study suggests a strategy for selecting a suitable platform for developing vaccines against MERS-CoV or other emerging coronaviruses.IMPORTANCE Coronavirus is an RNA virus with a higher mutation rate than DNA viruses. Therefore, a mutation in S-protein, which mediates viral infection by binding to a human cellular receptor, is expected to cause difficulties in vaccine development. Given that DNA-protein vaccines promote stronger cell-mediated immune responses than protein-only vaccination, we immunized mice with various combinations of DNA priming and protein boosting using the S-subunit sequences of the MERS-CoV EMC/2012 strain. We demonstrated a cross-protective effect against wild-type KOR/KNIH/002, a strain with two mutations in the S amino acids, including one in its RBD. The vaccine also provided cross-neutralization against 15 different S-pseudotyped viruses. These suggested that a vaccine targeting one variant of S can provide cross-protection against multiple viral strains with mutations in S. The regimen of DNA priming/Protein boosting can be applied to the development of other coronavirus vaccines.
Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Proteção Cruzada , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas de DNA/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Feminino , Humanos , Imunidade Celular , Imunização Secundária , Imunogenicidade da Vacina , Camundongos , Plasmídeos/administração & dosagem , Plasmídeos/genética , Plasmídeos/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Vacinação , Vacinas de DNA/administração & dosagem , Vacinas Virais/administração & dosagemRESUMO
Apigenin (4',5,7-trihydroxyflavone, flavonoid) is a phenolic compound that is known to reduce the risk of chronic disease owing to its low toxicity. The first study on apigenin analyzed its effect on histamine release in the 1950s. Since then, anti-mutation and antitumor properties of apigenin have been widely reported. In the present study, we evaluated the apigenin-mediated amelioration of skin disease and investigated its applicability as a functional ingredient, especially in cosmetics. The effect of apigenin on RAW264.7 (murine macrophage), RBL-2H3 (rat basophilic leukemia), and HaCaT (human immortalized keratinocyte) cells were analyzed. Apigenin (100 µM) significantly inhibited nitric oxide (NO) production, cytokine expression (interleukin (IL)-1ß, IL6, cyclooxygenase (COX)-2, and inducible nitric oxide synthase [iNOS]), and phosphorylation of mitogen-activated protein kinase (MAPK) signal molecules, including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK) in RAW264.7 cells. Apigenin (30 M) also inhibited the phosphorylation of signaling molecules (Lyn, Syk, phospholipase Cγ1, ERK, and JNK) and the expression of high-affinity IgE receptor FcεRIα and cytokines (tumor necrosis factor (TNF)-α, IL-4, IL-5, IL-6, IL-13, and COX-2) that are known to induce inflammation and allergic responses in RBL-2H3 cells. Further, apigenin (20 µM) significantly induced the expression of filaggrin, loricrin, aquaporin-3, hyaluronic acid, hyaluronic acid synthase (HAS)-1, HAS-2, and HAS-3 in HaCaT cells that are the main components of the physical barrier of the skin. Moreover, it promoted the expression of human ß-defensin (HBD)-1, HBD-2, HBD-3, and cathelicidin (LL-37) in HaCaT cells. These antimicrobial peptides are known to play an important role in the skin as chemical barriers. Apigenin significantly suppressed the inflammatory and allergic responses of RAW264.7 and RBL cells, respectively, and would, therefore, serve as a potential prophylactic and therapeutic agent for immune-related diseases. Apigenin could also be used to improve the functions of the physical and chemical skin barriers and to alleviate psoriasis, acne, and atopic dermatitis.
Assuntos
Apigenina/farmacologia , Dermatopatias/tratamento farmacológico , Animais , Antialérgicos/metabolismo , Antialérgicos/farmacologia , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Apigenina/metabolismo , Linhagem Celular , Citocinas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Filagrinas , Células HaCaT/efeitos dos fármacos , Humanos , Imunoglobulina E/metabolismo , Interleucina-1beta/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Mastócitos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação/efeitos dos fármacos , Células RAW 264.7/efeitos dos fármacos , Ratos , Receptores de IgE/genética , Transdução de Sinais/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/metabolismo , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Resolution of inflammation is important for physiological homeostasis. Chronic inflammatory diseases may be caused by abnormal resolution of inflammation. However, what causes a failure of inflammatory resolution is unclear. Here we investigated the involvement of high mobility group box 1 (HMGB1) protein in the control of inflammatory resolution as an 'anti-resolution factor'. We first confirmed the increased expression of HMGB1 and prostaglandin reductase 1 (PTGR1) in inflammatory conditions and HMGB1-mediated regulation of the expression of PTGR1. The inhibition of phagocytosis by HMGB1 was abrogated by PTGR1 silencing. PTGR1 was a direct target of miR522-3p and its expression was regulated by miRNA-522-3p inhibitor or mimic. Finally, miR-522-3p had an important role in the regulation of PTGR1 expression by HMGB1. The data indicates that HMGB1-miR-522-3p-PTGR1 axis may be involved in the abnormal resolution of inflammation and suggests that this mechanism might be a target for modulation of chronic inflammatory disorder.
Assuntos
Oxirredutases do Álcool/genética , Proteína HMGB1/genética , Macrófagos/metabolismo , MicroRNAs/genética , Fagocitose/genética , Oxirredutases do Álcool/antagonistas & inibidores , Oxirredutases do Álcool/metabolismo , Sequência de Bases , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Regulação da Expressão Gênica , Proteína HMGB1/metabolismo , Humanos , Inflamação , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Monócitos/citologia , Monócitos/metabolismo , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Fagocitose/efeitos dos fármacos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
This study aimed to validate body composition analysis using bioelectrical impedance analysis (BIA) against dual-energy X-ray absorptiometry (DXA) in children with obesity and to compare agreement between BIA and DXA according to their degree of obesity. Three hundred and sixteen children aged 6-17 years participated in the Intervention for Childhood and Adolescents Obesity via Activity and Nutrition study. We divided participants by body mass index (BMI) percentile (group 1: mild to moderate obesity; group 2: severe obesity) and compared body composition variables, eg, percentage of body fat (%BF), fat mass (FM), and fat-free mass (FFM) using BIA and DXA. The %BF and FM of BIA were significantly lower (-1.8% and -0.8 kg, respectively), and the FFM of BIA was significantly higher (1.4 kg) than those of DXA. There were significant negative relationships between the absolute value of differences from BIA and DXA and BMI z-scores in %BF, FM, and FFM (regression coefficient [ß]: -1.39, 95% confidence interval [CI]: -1.81 to -0.97; ß: -0.34, 95%CI: -0.61 to -0.06; ß: -0.73, 95%CI: -1.03 to -0.44, respectively). The gap of body compositions between BIA and DXA decreased as participants became more obese, and the differences of FM in boys with severe obesity and the differences of %BF and FFM in girls with severe obesity were much less than those in children with mild to moderate obesity. In conclusion, the agreement between DXA and BIA was better for children with severe obesity than for children with mild to moderate obesity.
Assuntos
Composição Corporal , Impedância Elétrica , Obesidade Mórbida/fisiopatologia , Obesidade Infantil/fisiopatologia , Absorciometria de Fóton , Adiposidade , Adolescente , Índice de Massa Corporal , Criança , Feminino , Humanos , MasculinoRESUMO
High-mobility group box 1 (HMGB1) enhances inflammatory reactions by potentiating the activity of pro-inflammatory mediators and suppressing the phagocytosis of apoptotic neutrophils. However, the effects of HMGB1 on phagocytosis induced by pro-resolving mediators, such as resolvins, have not been studied up until this point. In this study, we investigated the effects and underlying mechanism of HMGB1 on resolvin D1-induced phagocytosis of MDA-MB-231 cells, which were selected as a model system based on their phagocytic capability and ease of transfecting them with a plasmid or siRNA in several cancer cell lines. Then we confirmed effects of HMGB1 in THP-1 cells. Resolvin D1 (RvD1) enhanced phagocytosis in MDA-MB-231 and THP-1 cells. HMGB1 suppressed RvD1-induced phagocytosis in MDA-MB.231 and THP-1 cells. HMGB1 dose-dependently induced the expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the inactivating enzyme in pro-resolving lipid mediators such as RvE1 and RvD1. Involvement of 15-PGDH in-HMGB-1-induced suppression of phagocytosis was examined using siRNA of 15-PGDH or 15-PGDH inhibitor, TD23. Surprisingly, the silencing of 15-PGDH increased phagocytotic activity of MDA-MB-231 cells. TD23 also enhanced phagocytosis of MDA-MB-231 and THP-1 cells. In conclusion, the release of HMGB1 during the inflammatory phase induces 15-PGDH expression, which suppresses the phagocytotic activity of macrophages. These processes might be involved in the mechanism that blocks the resolution of inflammation, thereby allowing acute inflammation to progress to chronic inflammation.
RESUMO
BACKGROUND: A low serum level of high-density lipoprotein cholesterol (HDL-C) is a risk factor for cardiovascular disease. Proprotein convertase subtilisin/kexin type 5 (PCSK5) modulates HDL-C metabolism through the inactivation of endothelial lipase activity. METHODS: Therefore, we analysed the effects of PCSK5 on HDL-C and investigated the association between genetic variation in PCSK5 and dietary polyunsaturated fatty acids (PUFAs) intakes in Korean adults and children. This population-based study which was conducted in South Korea included 4205 adults (43% male) aged 40-69â years and 1548 children (48.6% boys) aged 8-13â years. Dietary intake was assessed using a semiquantitative food frequency questionnaire in adults and modified 3-day food records in children. RESULTS: After adjustments for age and body mass index, we identified a significant association between SNP rs1029035 of the PCSK5 gene and HDL-C concentrations specifically for men in both populations (adults, p=0.004; children, p=0.003; meta, p=7×10(-4)). Additionally, the interaction between the PCSK5 rs1029035 genotype and dietary polyunsaturated fatty acids intake influenced serum HDL-C concentrations in men (adults, p=0.001; children, p=0.008). The deleterious effect of the C allele on serum HDL-C was present only when dietary PUFA intake was less than the dichotomised median level (adults, p=0.011; children, p=0.001). Serum HDL-C concentrations were decreased in men with the C allele genotype and low consumption of dietary PUFA including n-3 and n-6. CONCLUSION: According to these results, men carrying of the C allele were associated with low HDL-C concentrations and might exert beneficial effects on HDL-C concentrations following consumption of a high-PUFA diet.
Assuntos
HDL-Colesterol/genética , Dieta , Ácidos Graxos Insaturados/metabolismo , Variação Genética , Adulto , Idoso , Criança , Ingestão de Energia , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Pró-Proteína Convertase 5 , República da CoreiaRESUMO
BACKGROUND: The current study aimed to screen for relationships and different potential metabolic biomarkers involved between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) in adolescents. METHODS: The study included 148 obese adolescents aged between 14 and 16. The study participants were divided into MUO and MHO groups based on the age-specific adolescent metabolic syndrome (MetS) criteria of the International Diabetes Federation. The current study was conducted to investigate the clinical and metabolic differences between the MHO and MUO groups. Multivariate analyses were conducted to investigate the metabolites as independent predictors for the odds ratio and the presence of the MetS. RESULTS: There were significant differences in the three acylcarnitines, five amino acids, glutamine/glutamate ratio, three biogenic amines, two glycerophospholipids, and the triglyceride-glucose index between the MUO group and those in the MHO group. Moreover, several metabolites were associated with the prevalence of MUO. Additionally, several metabolites were inversely correlated with MHO in the MUO group. CONCLUSIONS: In this study, the biomarkers found in this study have the potential to reflect the clinical outcomes of the MUO group. These biomarkers will lead to a better understanding of MetS in obese adolescents.
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Scrub typhus is an acute febrile, mite-borne disease endemic to the Asia-Pacific region. In South Korea, it is a seasonal disease that occurs frequently in the autumn, and its incidence has increased steadily. In this study, we used a liquid chromatography and flow injection analysis-tandem mass spectrometry-based targeted urine metabolomics approach to evaluate the host response to Orientia tsutsugamushi infection. Balb/c mice were infected with O. tsutsugamushi Boryong, and their urine metabolite profile was examined. Metabolites that differed significantly between the experimental groups were identified using the Kruskal-Wallis test. Sixty-five differential metabolites were identified. The principal metabolite classes were acylcarnitines, glycerophospholipids, biogenic amines, and amino acids. An ingenuity pathway analysis revealed that several toxic (cardiotoxic, hepatotoxic, and nephrotoxic) metabolites are induced by scrub typhus infection. This is the first report of urinary metabolite biomarkers of scrub typhus infection and it enhances our understanding of the metabolic pathways involved.
Assuntos
Ácaros , Orientia tsutsugamushi , Tifo por Ácaros , Animais , Camundongos , Tifo por Ácaros/epidemiologia , Ásia , República da CoreiaRESUMO
BACKGROUND: Glutamate is a major neurotransmitter, although it causes cytotoxicity and inflammation in nonneuronal organs. This study aimed to investigate the metabolic disorders in which glutamate, associated with type 2 diabetes onset, is induced in the liver. METHODS: An analysis of Korean community-based Ansan-Ansung cohort study data as well as functional research using in vitro and mouse models were performed. RESULTS: Groups with high plasma glutamate levels (T2, T3) had a significantly increased risk of diabetes incidence after 8 years, compared to the group with relatively low glutamate levels (T1). Analysis of the effect of glutamate on diabetes onset in vitro showed that glutamate induces insulin resistance by increasing glucose-related protein 78 (GRP78) and phosphoenolpyruvate carboxykinase (PEPCK) expression in SK-Hep-1 human liver cells. In addition, three different genes, FRMB4B, PLG, and PARD3, were significantly associated with glutamate and were identified via genome-wide association studies. Among glutamate-related genes, plasminogen (PLG) levels were most significantly increased in several environments in which insulin resistance was induced, and was also upregulated by glutamate. Glutamate-induced increase in PLG in liver cells was caused by metabotropic glutamate receptor 5 activation, and PLG levels were also upregulated after extracellular secretion. Moreover, glutamate increased the expression of plasminogen activator inhibitor-1 (PAI-1). Thus, extracellular secreted PLG cannot be converted to plasmin (fibrinolytic enzyme) by increased PAI-1. CONCLUSIONS: Increased glutamate is closely associated with the development of diabetes, and it may cause metabolic disorders by inhibiting the fibrinolytic system, which plays an important role in determining blood clots, a hallmark of diabetes.
Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Camundongos , Animais , Humanos , Plasminogênio/genética , Plasminogênio/metabolismo , Inibidor 1 de Ativador de Plasminogênio , Ácido Glutâmico , Diabetes Mellitus Tipo 2/genética , Resistência à Insulina/genética , Estudos de Coortes , Estudo de Associação Genômica Ampla , República da Coreia/epidemiologiaRESUMO
To investigate the role of genetic predisposition in the pathogenesis of polycystic ovary syndrome (PCOS) in relation to obesity, we performed a genome-wide association study of PCOS in Koreans (n=1741). PCOS is a heterogeneous endocrinal disorder of uncertain etiology. Obesity is one of the well-known risk factors for PCOS. Genome-wide association study. Women with or without PCOS. A total of 1881 samples were genotyped using Illumina HumanOmni1 Quad v1 and processed by R packages. The PCOS patients were divided into two subgroups according to PCOS diagnostic criteria (Rotterdam and National Institutes of Health (NIH)). For PCOS-associated loci in the two definitions, we successfully confirmed significant associations of GYS2 for body mass index in the discovery stage. We further replicated pleiotropic associations of GYS2 in a childhood obesity study (n=482) and in a gestational diabetes study (n=1710), respectively. Our study provides a preliminary framework upon diverse genetic effects underlying PCOS in Korean women. A newly identified GYS2 gene as a predisposing factor of PCOS might expand understanding of the biological pathways in metabolic and endocrine regulation.
Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Obesidade/genética , Síndrome do Ovário Policístico/genética , Adulto , Amenorreia/genética , Povo Asiático , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Diabetes Gestacional/genética , Feminino , Frequência do Gene , Pleiotropia Genética , Humanos , Oligomenorreia/genética , Síndrome do Ovário Policístico/diagnóstico , Polimorfismo de Nucleotídeo Único , Gravidez , Fatores de Risco , Adulto JovemRESUMO
Previous studies have reported a relationship between short sleep duration and childhood overweight. Although school-aged children tend to compensate for weekday sleep deficit by increasing weekend sleep duration, the association between weekend catch-up sleep and childhood overweight remains unclear. This study aimed to examine the relationship between weekend catch-up sleep and being overweight in children. A total of 936 school children (48.2% boys) aged 10 or 11 years participated in this school-based cohort study. Anthropometric measurements including height and body weight were carried out. We obtained data on sleep patterns, lifestyle and parent characteristics using questionnaires. The main outcome measure was childhood overweight. After adjusting for the relevant confounding variables (age, sex, breakfast eating, screen time and parental obesity), longer sleep on weekdays and weekends was associated with decreased odds of childhood overweight (OR: 0.68; 95% CI: 0.54-0.86; OR: 0.64; 95% CI: 0.53-0.77, respectively). Participants with increased catch-up sleep duration during weekends also had decreased odds of being overweight (OR: 0.67; 95% CI: 0.53-0.85). There was an interaction between weekday sleep duration and weekend catch-up sleep in relation to childhood overweight, and this effect of weekend catch-up sleep on being overweight was stronger as the participants slept less on weekdays (P = 0.024). These results indicate that weekend catch-up sleep is independently associated with decreased risk of being overweight in fifth-grade students, and this effect can be varied by the weekday sleep duration. A prospective study is required to confirm this observation.
Assuntos
Sobrepeso/prevenção & controle , Sobrepeso/fisiopatologia , Privação do Sono/prevenção & controle , Privação do Sono/fisiopatologia , Sono/fisiologia , Adulto , Desjejum , Criança , Feminino , Humanos , Masculino , Obesidade/fisiopatologia , Obesidade/prevenção & controle , Razão de Chances , Pais , Inquéritos e QuestionáriosRESUMO
Alcohol consumption is associated with a high increased lipid profile and this association may depend on genetic risk factors. In this study, we aimed to assess the effects of genetic variation associated with alcohol consumption on lipid profiles using data from two Korean population studies. We performed a genotype association study using the HEXA (n = 51,349) and KNHANES (n = 9158) data. Genotype analyses of the two sets of Korean population data showed associations of increased total cholesterol and high-density lipoprotein (HDL)-cholesterol with CETP rs708272. The HEXA and KNHANES populations revealed differences in HDL cholesterol according to the presence of CETP rs708272, independent of ALDH2 rs671 and alcohol consumption. In contrast, total cholesterol levels were associated with alcohol consumption and ALDH2 rs671 in men with CETP rs708272 (CT and TT genotypes). Furthermore, in drinkers with ALDH2 rs671 (GA and AA genotypes), higher total cholesterol was associated with the CETP rs708272 TT minor homozygous genotype based on both HEXA and KNHANES data. Our findings demonstrated that alcohol consumption and genetic variation in either CETP or ALDH2 may be associated with cholesterol levels. We hope these findings will provide a better understanding of the relationship between alcohol consumption and cholesterol according to each individual's genetic background.
Assuntos
Consumo de Bebidas Alcoólicas , Polimorfismo Genético , Consumo de Bebidas Alcoólicas/genética , Aldeído-Desidrogenase Mitocondrial/genética , Colesterol , Proteínas de Transferência de Ésteres de Colesterol/genética , HDL-Colesterol/genética , Genótipo , Humanos , MasculinoRESUMO
BACKGROUND: We investigated the relationship among socioeconomic status factors, the risk of anemia, and iron deficiency among school-aged children in Korea. METHODS: The sample consisted of fourth-grade students aged 10 y recruited from nine elementary schools in Korean urban areas in 2008 (n = 717). Anthropometric and blood biochemistry data were obtained for this cross-sectional observational study. Anemia was defined as hemoglobin levels lower than 11.5 g/dl. Iron deficiency was defined as serum iron levels lower than 40 ug/dl. We also obtained data on parental education from questionnaires and on children's diets from 3-day food diaries. Parental education was categorized as low or high, with the latter representing an educational level beyond high school. RESULTS: Children with more educated mothers were less likely to develop anemia (P = 0.0324) and iron deficiency (P = 0.0577) than were those with less educated mothers. This group consumed more protein (P = 0.0004) and iron (P = 0.0012) from animal sources than did the children of less educated mothers, as reflected by their greater consumption of meat, poultry, and derivatives (P < 0.0001). Logistic regression analysis revealed a significant inverse relationship between maternal education and the prevalence of anemia (odds ratio: 0.52; 95% confidence interval: 0.32, 0.85). CONCLUSIONS: As a contributor to socioeconomic status, maternal education is important in reducing the risk of anemia and iron deficiency and in increasing children's consumption of animal food sources.
Assuntos
Anemia Ferropriva/epidemiologia , Dieta , Mães , Adolescente , Anemia Ferropriva/sangue , Criança , Estudos Transversais , Registros de Dieta , Escolaridade , Feminino , Humanos , Masculino , República da Coreia/epidemiologia , Classe SocialRESUMO
Trimethylamine N-oxide (TMAO) and its precursors, including choline, betaine, and L-carnitine, are gut microbiota-related metabolites associated with the risk of obesity. We aimed (1) to comprehensively examine whether the changes in plasma TMAO and its precursors induced by lifestyle intervention are associated with the improvements in plasma metabolic parameters; and (2) to identify the fecal microbiome profiles and nutrient intakes associated with these metabolites and metabolic index. Data from 40 participants (obese children and adolescents) having the plasma metabolites data related to the changes in BMI z-scores after 6-month lifestyle intervention were analyzed. In this study, we observed that choline and the betaine-to-choline ratio (B/C) showed different patterns depending on the changes in BMI z-scores by the response to lifestyle intervention. During the 6 months, an increase in choline and a decrease in B/C were observed in non-responders. We also found that changes in choline and B/C were associated with the improvements in plasma lipid levels. Individuals who showed reduced choline or increased B/C from the baseline to 6 months had a significant decrease in LDL-cholesterol over 6 months compared to those with increased choline or decreased B/C, respectively. In addition, the increase in choline or decrease in B/C was associated with the increase in plasma triglycerides. The distribution of gut microbiota belonging to the Firmicutes, such as Clostridia, Clostridiales, Peptostreptococcaceae, Romboutsia, and Romboutsia timonensis was altered to be lower during the 6 months both as choline decreased and B/C increased. Moreover, the decrease in choline and the increase in B/C were associated with reduced fat intake and increased fiber intake after the 6-month intervention. Finally, lower abundance of Romboutsia showed the association with lower LDL-cholesterol and higher intake of fiber. In summary, we demonstrated that reduced choline and increased B/C by lifestyle intervention were associated with the improvements of LDL-cholesterol and triglycerides, low-fat and high-fiber intakes, and low abundance of Firmicutes. These indicate that changes to circulating choline and B/C could predict individuals' changes in metabolic compositions in response to the lifestyle intervention.
Assuntos
Betaína/sangue , Colina/sangue , Microbioma Gastrointestinal/fisiologia , Estilo de Vida , Metabolismo dos Lipídeos , Lipídeos/sangue , Adolescente , Bactérias/classificação , Betaína/metabolismo , Carnitina/sangue , Criança , Colina/metabolismo , Clostridiales , Ingestão de Alimentos , Fezes/microbiologia , Firmicutes , Microbioma Gastrointestinal/genética , Humanos , Metilaminas , Nutrientes , Obesidade Infantil , RNA Ribossômico 16S/genéticaRESUMO
Potassium voltage-gated channel subfamily Q member 1 (KCNQ1) is one of the strongest susceptibility genes for type 2 diabetes mellitus (T2DM). Association studies between KCNQ1 genetic variants and T2DM have been reported. The multifactorial disease T2DM is caused by interactions between genetic susceptibility and environmental factors. In this study, we examined the associations between the KCNQ1 haplotype, which consists of the major alleles rs3852528, rs11024175, and rs2237892 (ht: ACC), and environmental factors such as alcohol consumption, which are related to the risk of T2DM, in two independent Korean populations. Data from health examination studies, i.e., HEXA (n = 50,357 subjects) and the Ansung-Ansan community-based Korean cohort study (n = 7603), were analyzed. In both cohorts, fasting blood glucose levels were significantly increased in moderate-to-heavy drinkers and carriers of the homozygous ACC haplotype. A significant association between the KCNQ1 haplotype and alcohol consumption in the risk of diabetes was observed in the HEXA (OR 1.587; 95% CI 1.128-2.234) and Ansung-Ansan (OR 2.165; 95% CI 1.175-3.989) cohorts compared with abstainers not carrying the KCNQ1 haplotype. Associations of the KCNQ1 haplotype with alcohol consumption and ß-cell function were observed in the Ansung-Ansan cohort. Moderate-to-heavy drinkers with the ACC haplotype had lower fasting insulin levels and mean 60 min insulinogenic index (IGI60) compared with light drinkers and abstainers not carrying the ACC haplotype. These findings indicate that KCNQ1 variants play a synergistic role with alcohol consumption in the development of T2DM and impaired ß-cell function.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Diabetes Mellitus Tipo 2/etiologia , Canal de Potássio KCNQ1/genética , Alcoolismo/complicações , Alelos , Glicemia/análise , Diabetes Mellitus Tipo 2/genética , Feminino , Predisposição Genética para Doença/genética , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , República da CoreiaRESUMO
Chronic alcohol consumption is known to be associated with type 2 diabetes (T2D), which is developed by two underlying mechanisms, ß-cell dysfunction and insulin resistance. Identification of genetic variants in association with the development of T2D may help explain the genetic risk factors of T2D. In this study, we tried to find out some genetic variations, which interact with alcohol consumption and also are associated with ß-cell function through 12 year's follow-up study in Korean population. We performed a genotype association study using the community-based Ansung-Ansan Cohort data (baseline n = 3120; follow-up n = 433). Genotype association analyses of the baseline data showed that alcohol consumption is associated with the decreases of blood insulin levels and insulin secretion in participants with the KCNJ11 rs5219 risk allele. Moreover, multivariate logistic regression analyses revealed that the risk allele group is vulnerable to impairment of ß-cell function in response to alcohol consumption (OR 1.450; 95% CI 1.061-1.982). Furthermore, 12-year' follow-up results showed that alcohol consumption synergistically decreases insulin secretion in participants with KCNJ11 rs5219 risk alleles. Our findings demonstrate that the KCNJ11 rs5219 risk allele in combination with alcohol consumption could be a potential risk factor of ß-cell dysfunction. We hope that this new findings could be helpful to further understand the development of T2D depending on individual genetic background in association with alcohol consumption.