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1.
Korean Circ J ; 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32812402

RESUMO

BACKGROUND AND OBJECTIVES: Associations between blood lipids and risk of ischemic heart disease (IHD) have been reported in observational studies. However, due to confounding and reverse causation, observational studies are influenced by bias, thus their results show inconsistency in the effects of lipid levels on IHD. In this study, we evaluate whether lipid levels have an effect on the risk of IHD in a Korean population. METHODS: A 2-sample Mendelian randomization (MR) study, using the genetic variants associated with lipid levels as the instrumental variables was performed. Genetic variants significantly associated with lipid concentrations were obtained from the Korean Genome and Epidemiology Study (n=35,000), and the same variants on IHD were obtained from the Korean Cancer Prevention Study-II (n=13,855). Inverse variance weighting (IVW), weighted median, and MR-Egger approaches were used to assess the causal association between lipid levels and IHD. Radial MR methods were applied to remove outliers subject to pleiotropic bias. RESULTS: Causal association between low-density lipoprotein-cholesterol (LDL-C) and IHD was observed in the IVW method (odds ratio, 1.013; 95% confidence interval, 1.007-1.109). However, high-density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) did not show causal association with IHD. In the Radial MR analysis of the relationship between HDL-C, TG and IHD, outliers were detected. Interestingly, after removing the outliers, a causal association between TG and IHD was found. CONCLUSIONS: High levels LDL-C and TG were causally associated with increased IHD risk in a Korean population, these results are potentially useful as evidence of a significant causal relationship.

2.
BMC Med Genet ; 21(1): 160, 2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807123

RESUMO

BACKGROUND: Diabetes is mostly assessed by the fasting glucose level. Several studies reported that serum fasting glucose levels and cardiovascular disease are associated with MC4R. METHODS: A total of 4294 subjects participated in this study. There were 1810 subjects with cardiovascular disease among the 4294 subjects. We used multivariate linear regression models and multiple logistic regression analysis. RESULTS: Individuals with the TC/CC genotype had a 1.29-fold higher risk of diabetes than did those with the TT genotype when adjusting for age, sex, and BMI (OR, 1.29; 95% CI, 1.04-1.60). For healthy subjects, the association was significant in women (OR, 1.99; 95% CI, 1.01-3.93). Men with the TC/CC genotype had a 1.21-fold higher risk of cardiovascular disease than did those with the TT genotype when adjusting for age, sex, and BMI (OR, 1.21; 95% CI, 1.04-1.41). The relationship between MC4R and cardiovascular disease was stronger in lean men (OR, 1.40; 95% CI, 1.12-1.74, p = 0.0028) than in overweight men. CONCLUSIONS: This study suggests that the rs17782313 SNP in MC4R is related to diabetes and the SNP is also associated with cardiovascular disease in lean men.


Assuntos
Doenças Cardiovasculares/genética , Diabetes Mellitus Tipo 2/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Receptor Tipo 4 de Melanocortina/genética , Glicemia/metabolismo , Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Razão de Chances , República da Coreia
3.
Sci Rep ; 10(1): 13075, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32753590

RESUMO

Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD); however, more than 25% of COPD patients are non-smokers, and gene-by-smoking interactions are expected to affect COPD onset. We aimed to identify the common genetic variants interacting with pack-years of smoking on FEV1/FVC ratios in individuals with normal lung function. A genome-wide interaction study (GWIS) on FEV1/FVC was performed for individuals with FEV1/FVC ratio ≥ 70 in the Korea Associated Resource cohort data, and significant SNPs were validated using data from two other Korean cohorts. The GWIS revealed that rs10947231 and rs8192575 met genome-wide significant levels; For [Formula: see text] the likelihood ratio (LR) test was conducted, and its P values, PLR, for rs10947231 and rs8192575 were 2.23 × 10-12 and 1.18 × 10-8, respectively. Interaction between rs8192575 and smoking is significantly replicated with two additional data (PINT = 0.0454, 0.0131). Expression quantitative trait loci, topologically associated domains, and PrediXcan analyses revealed that rs8192575 is significantly associated with AGER expression. SNPs on the 6p21 region are associated with FEV1/FVC, and the effect of smoking on FEV1/FVC differs among the associated genotypes.


Assuntos
Cromossomos Humanos Par 6/genética , Estudo de Associação Genômica Ampla , Pulmão/fisiopatologia , Fumar/efeitos adversos , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Locos de Características Quantitativas/genética
4.
Environ Sci Pollut Res Int ; 27(27): 34300-34310, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32557043

RESUMO

Previous studies of urinary bisphenol A (BPA), phthalate metabolites, and obesity risk have shown inconsistent results. Menopausal status is one of the main factors that affect hormone secretion change in women. In this study, we examined whether urinary BPA and phthalate metabolite levels are associated with obesity and whether the associations differ by sex and menopausal status in a sample of Korean adult populations. We recruited participants at three branches (Yeouido, Gangnam, and Gwanghwamun) of the Korea Medical Institute, a nationwide health check-up center, from 2015 to 2016. Urinary BPA level was measured by high-performance liquid chromatography-tandem mass spectrometry (Agilent 6490 Triple Quad LC-MS/MS; Agilent Technologies, CA, USA). Urinary six phthalate metabolites were analyzed with ultra-high-performance liquid chromatography-tandem mass spectrometry (TSQ Quantum Access Mass; Thermo Fisher Scientific, MA, USA). Participants with body mass index ≥ 25 kg/m2 were defined as general obesity group. Men with waist circumference (WC) ≥ 90 cm and women with WC ≥ 85 cm were defined as abdominal obesity group. Age, sex, alcohol intake, smoking, and exercise were considered in multivariate logistic regression models. Among the total of 702 participants, 211 participants were classified into the general obesity group, and 131 participants were classified into the abdominal obesity group. Urinary phthalate metabolite levels were not associated with general and abdominal obesity in men and women. However, in women, urinary BPA concentration was positively associated with abdominal obesity (OR = 1.50, 95% CI 1.00-2.26). Also, the association was stronger in postmenopausal women (OR = 2.23, 1.01-4.92), while it was weak in premenopausal women (OR = 1.31, 0.78-2.20). In this study, urinary BPA concentration was associated with abdominal obesity in women, especially postmenopausal women. Future studies should consider sex and menopausal status when investigating associations between urinary BPA, phthalate metabolites levels, and obesity.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Adulto , Compostos Benzidrílicos , Cromatografia Líquida , Feminino , Humanos , Masculino , Obesidade , Fenóis , República da Coreia , Espectrometria de Massas em Tandem
5.
Eur J Clin Invest ; 50(10): e13300, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32474920

RESUMO

BACKGROUND: Observational studies have shown that high levels of serum uric acid (UA) were associated with atrial fibrillation (AF). However, the causal effect of urate on the risk of AF is still unknown. To clarify the potential causal association between UA and AF, we performed a Mendelian randomization (MR) analysis using genetic instrumental variables (IVs). MATERIALS AND METHODS: From the Korean GWAS dataset of 633 patients with AF (mean age 50.6 ± 7.8 years, 80.9% male, Yonsei AF Ablation cohort) who underwent radiofrequency catheter ablation and the data from 3533 controls (from the Korea Genome Epidemiology Study), we selected 9 SNPs, with a P value less than .05, associated with an increased UA serum level. Additionally, we calculated the weighted genetic risk score (wGRS) using the selected 9 SNPs, to use it as an instrumental variable. A Mendelian randomization analysis was calculated by a 2-stage estimator method. RESULTS: The conventional association between the serum UA and AF was significant (P = .001) after adjusting for potential confounding factors. The SNP rs1165196 on SLC17A1 (F-statistics = 208.34, 0.18 mg/mL per allele change, P < .001) and wGRS (F-statistics = 222.26, 0.20 mg/mL per 1SD change, P < .001) were significantly associated with an increase in the UA level. The MR analysis was causally associated with rs1165196 (estimated odds ratio (OR), 0.21, 95% confidence interval (CI), 0.06-0.75, P = .017), but not wGRS (estimated OR, 1.07, 95% CI, 0.57-2.01, P = .832). CONCLUSION: The serum UA level was independently associated with the AF risk.

6.
J Hum Genet ; 65(10): 813-821, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32409696

RESUMO

A prolonged PR interval predicts atrial fibrillation (AF) recurrence after catheter ablation. We investigated the causal association between the PR interval and AF clinical recurrence by a Mendelian randomization. We prospectively included 1722 patients with AF (73.2% male, 58.6 ± 10.8 years old, 71.3% paroxysmal AF) who underwent catheter ablation into a genome-wide association study (GWAS). We searched for the genetic associations between the PR interval and AF recurrence by analyzing 44 single nucleotide polymorphisms (SNPs) already known to be associated with the PR interval, and investigated the Mendelian randomization. Based on the quartile analysis, the highest quartile of the PR interval was associated with an increased risk of AF recurrence compared with the lowest quartile (Hazard ratio (HR) = 1.91, 95% CI = 1.51-2.42, P = 8.41 × 10-8) during 35.7 ± 28.5 months of follow-up. Among 44 SNPs known to be associated with the PR interval, two SNPs had significant associations with the PR interval (P < 0.001 for each SNP). CAV1 (HR = 1.15, 95% CI = 1.02-1.31, P = 0.024) was associated with clinical recurrence of AF. A Mendelian randomization analysis demonstrated a significant association with CAV1 (HR = 1.04, 95% CI = 1.01-1.07, P = 0.006). A prolonged PR interval was a risk factor for an AF recurrence, and the PR interval had a potentially causal association with an AF clinical recurrence after catheter ablation at the genetic level.

7.
Cancer Epidemiol Biomarkers Prev ; 29(6): 1271-1277, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32245787

RESUMO

BACKGROUND: Risk prediction models may be useful for precision breast cancer screening. We aimed to evaluate the performance of breast cancer risk models developed in European-ancestry studies in a Korean population. METHODS: We compared discrimination and calibration of three multivariable risk models in a cohort of 77,457 women from the Korean Cancer Prevention Study (KCPS)-II. The first incorporated U.S. breast cancer incidence and mortality rates, U.S. risk factor distributions, and RR estimates from European-ancestry studies. The second recalibrated the first by using Korean incidence and mortality rates and Korean risk factor distributions, while retaining the European-ancestry RR estimates. Finally, we derived a Korea-specific model incorporating the RR estimates from KCPS. RESULTS: The U.S. European-ancestry breast cancer risk model was well calibrated among Korean women <50 years [expected/observed = 1.124 (0.989, 1.278)] but markedly overestimated the risk for those ≥50 years [E/O = 2.472 (2.005, 3.049)]. Recalibrating absolute risk estimates using Korean breast cancer rates and risk distributions markedly improved the calibration in women ≥50 [E/O = 1.018 (0.825, 1.255)]. The model incorporating Korean-based RRs had similar but not clearly improved performance relative to the recalibrated model. CONCLUSIONS: The poor performance of the U.S. European-ancestry breast cancer risk model among older Korean women highlights the importance of tailoring absolute risk models to specific populations. Recalibrating the model using Korean incidence and mortality rates and risk factor distributions greatly improved performance. IMPACT: The data will provide valuable information to plan and evaluate actions against breast cancer focused on primary prevention and early detection in Korean women.

8.
Analyst ; 145(5): 1695-1705, 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-31895365

RESUMO

We aimed to determine the serum concentrations of altered compounds to understand the changes in metabolism and pathophysiology that occur prior to thrombotic stroke. In this prospective cohort study, high-resolution metabolomics (HRM) was employed to analyze serum samples obtained from patients at risk of stroke (n = 99) and non-risk controls (n = 301). Partial least-squares discriminant analysis (PLS-DA), along with univariate analysis using a false discovery rate (FDR) of q = 0.05 were employed to identify the discriminant metabolic profiles and to determine significantly different metabolites between healthy control and stroke risk groups. PLS-DA satisfactorily separated the stroke risk sera from control sera. Additionally, these discriminant metabolic profiles were not related to hypertension, smoking, diabetes mellitus, or insulin sensitivity. A group of 35 metabolites, most of them amino acids, that were capable of discriminating stroke risk sera from controls were identified using untargeted metabolomics. Further, the targeted metabolomics approach confirmed that the quantified concentrations of l-tryptophan, 3-methoxytyramine, methionine, homocysteinesulfinic acid, cysteine, isoleucine, carnitine, arginine, linoleic acid, and sphingosine were specifically elevated in the sera of patients who were later diagnosed with stroke. Our untargeted and targeted metabolomics approaches support investigating these compounds as novel biomarkers for early and non-invasive detection of thrombotic stroke.


Assuntos
Biomarcadores/sangue , Acidente Vascular Cerebral/sangue , Trombose/sangue , Adulto , Estudos de Coortes , Análise Discriminante , Feminino , Humanos , Análise dos Mínimos Quadrados , Masculino , Metaboloma , Metabolômica , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico , Trombose/diagnóstico
9.
Arterioscler Thromb Vasc Biol ; 40(2): 437-445, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31801373

RESUMO

OBJECTIVE: A number of epidemiological studies have reported that decreased serum bilirubin, an endogenous antioxidant, is associated with cardiovascular disease. However, previous Mendelian randomization analyses conducted using a single sample have shown no evidence of association. Approach and Results: A 2-sample summary Mendelian randomization study was performed by obtaining exposure and outcome data from separate nonoverlapping samples. We utilized data from the KoGES (Korean Genome and Epidemiology Study; n=25 406) and KCPS-II (Korean Cancer Prevention Study-II; n=14 541) biobank for serum bilirubin and stroke, respectively. Using KoGES, a total of 1784 single nucleotide polymorphisms associated with serum bilirubin levels were discovered using a genome-wide significance threshold (P<5×10-8), of which 10 single nucleotide polymorphisms were identified as independent (R2<0.005) and adopted as genetic instruments. From KCPS-II, total and ischemic stroke cases were identified (n=1489 and n=686), with 12 366 acting as controls. Various 2-sample summary Mendelian randomization methods were employed, with Mendelian randomization estimates showing an inverse causal association between serum bilirubin levels and total stroke risk (odds ratio, 0.481 [95% CI, 0.234-0.988]; P=0.046). This association increased in magnitude when restricting the analysis to ischemic stroke cases (odds ratio, 0.302 [95% CI, 0.105-0.868]; P=0.026). CONCLUSIONS: Our findings provide evidence of significant causal relationship between high levels of bilirubin and decreased stroke risk in Korean population in agreement with observational approaches. This highlights the potential for bilirubin to serve as a therapeutic target for oxidative stress-related diseases such as stroke and suggests that previous findings were not a consequence of unmeasured confounding.


Assuntos
Bilirrubina/sangue , Isquemia Encefálica/sangue , Análise da Randomização Mendeliana/métodos , Adulto , Idoso , Biomarcadores/sangue , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , República da Coreia/epidemiologia , Fatores de Risco
10.
Diabetes Metab Res Rev ; 36(2): e3230, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31654550

RESUMO

BACKGROUND: We aimed to predict the incidence of obesity in a Korean population using a genetic risk score (GRS) constructed with obesity-related single nucleotide polymorphisms (SNPs) along with an oxidative stress score (OSS). METHODS: A total of 9460 Korean subjects and 356 974 SNPs were included. The GRS was constructed using three significant obesity-related SNP loci, and the OSS was calculated with three reliable oxidative stress biomarkers. RESULTS: The GRS showed a more significant association with increased obesity (OR = 2.879) than did individual SNPs after adjusting for age and sex. Three oxidative stress biomarkers, including malondialdehyde, oxidized low-density lipoprotein, and 8-epi-prostaglandin F2α , showed significantly high levels in the obese group. The OSS, which was the sum of each oxidative stress biomarker score, showed a markedly high association with the incidence of obesity, with an OR of 3.213. Based on the results of the regression tests and a receiver-operating characteristic (ROC) curve analysis, we found that HOMA-IR, high-sensitivity C-reactive protein (hs-CRP), the GRS, and the OSS were the most relevant factors for the increased risk of obesity and were significantly associated with the incidence of obesity. The area under the ROC curve was improved when the GRS was added to the model (from 74.2% to 75.1%). CONCLUSIONS: We first identified that subjects with an obesity GRS and a high OSS might have a higher risk of obesity. Our findings and weighting approaches were effective in predicting the incidence of obesity; furthermore, the GRS is a relevant factor that significantly predicts the risk of obesity.

11.
Cancer Epidemiol Biomarkers Prev ; 29(2): 477-486, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31826910

RESUMO

BACKGROUND: Risk variants identified so far for colorectal cancer explain only a small proportion of familial risk of this cancer, particularly in Asians. METHODS: We performed a genome-wide association study (GWAS) of colorectal cancer in East Asians, including 23,572 colorectal cancer cases and 48,700 controls. To identify novel risk loci, we selected 60 promising risk variants for replication using data from 58,131 colorectal cancer cases and 67,347 controls of European descent. To identify additional risk variants in known colorectal cancer loci, we performed conditional analyses in East Asians. RESULTS: An indel variant, rs67052019 at 1p13.3, was found to be associated with colorectal cancer risk at P = 3.9 × 10-8 in Asians (OR per allele deletion = 1.13, 95% confidence interval = 1.08-1.18). This association was replicated in European descendants using a variant (rs2938616) in complete linkage disequilibrium with rs67052019 (P = 7.7 × 10-3). Of the remaining 59 variants, 12 showed an association at P < 0.05 in the European-ancestry study, including rs11108175 and rs9634162 at P < 5 × 10-8 and two variants with an association near the genome-wide significance level (rs60911071, P = 5.8 × 10-8; rs62558833, P = 7.5 × 10-8) in the combined analyses of Asian- and European-ancestry data. In addition, using data from East Asians, we identified 13 new risk variants at 11 loci reported from previous GWAS. CONCLUSIONS: In this large GWAS, we identified three novel risk loci and two highly suggestive loci for colorectal cancer risk and provided evidence for potential roles of multiple genes and pathways in the etiology of colorectal cancer. In addition, we showed that additional risk variants exist in many colorectal cancer risk loci identified previously. IMPACT: Our study provides novel data to improve the understanding of the genetic basis for colorectal cancer risk.

12.
Metabolism ; 104: 154051, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31874143

RESUMO

BACKGROUND: Identifying changes in serum metabolites before the occurrence of acute myocardial infarction (AMI) is an important approach for finding novel biomarkers of AMI. METHODS: In this prospective cohort study, serum samples obtained from patients at risk of AMI (n = 112) and non-risk controls (n = 89) were tested using high-resolution metabolomics (HRM). Partial least-squares discriminant analysis (PLS-DA), along with univariate analysis using a false discovery rate (FDR) of q = 0.05 were performed to discriminate metabolic profiles and to determine significantly different metabolites between healthy control and AMI risk groups. RESULTS: PLS-DA significantly separated the AMI risk sera from control sera. The metabolites associated with amino acid biosynthesis, 2-oxocarboxylic acid, tryptophan, and amino sugar and nucleotide sugar metabolism pathways were mainly elevated in patients at risk of AMI. Further validation and quantification by MS/MS showed that tryptophan, carnitine, L-homocysteine sulfinic acid (L-HCSA), and cysteic acid (CA) were upregulated, while L-cysteine and L-cysteine sulfinic acid (L-CSA) were downregulated, specifically among AMI risk sera. Additionally, these discriminant metabolic profiles were not related to hypertension, smoking or alcoholism. CONCLUSION: In conclusion, detecting upregulated L-HCSA and CA along with carnitine among patients at risk for AMI could serve as promising non-invasive biomarkers for early AMI detection.


Assuntos
Carnitina/sangue , Ácido Cisteico/sangue , Homocisteína/análogos & derivados , Metabolômica , Infarto do Miocárdio/metabolismo , Idoso , Aminoácidos/metabolismo , Biomarcadores/sangue , Estudos de Coortes , Feminino , Homocisteína/sangue , Humanos , Análise dos Mínimos Quadrados , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Estudos Prospectivos , Medição de Risco , Fatores de Risco
13.
Front Physiol ; 10: 1421, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31803070

RESUMO

Liver cirrhosis (LC) is the final usual outcome of liver damage induced by various chronic liver diseases. Because of asymptomatic nature of LC, it is usually diagnosed at late and advanced stages, and patients are easy to miss the best timing for treatment. Thus, the early detection of LC is needed. In the prospective Korean Cancer Prevention Study-II (K-II), we aimed to identify valuable biomarkers for LC using metabolomics to distinguish subjects with incident LC (LC group) from subjects free from LC (control group) during a mean 7-year follow-up period. Metabolic alterations were investigated using baseline serum specimens acquired from 94 subjects with incident LC and 180 age- and sex-matched LC-free subjects via ultra-performance liquid chromatography (UPLC)-linear-trap quardrupole (LTQ)-Orbitrap mass spectrometry (MS). As a result of the metabolic analysis, 46 metabolites were identified. Among them, 11 and 18 metabolite level showed a significant increase and decrease, respectively, in the LC group compared to the control group. Nine metabolic pathways, including glyoxylate and dicarboxylate metabolism, amino acid metabolism, fatty acid metabolism, linoleic acid metabolism, α-linolenic acid metabolism, and arachidonic acid metabolism, were significantly different between the two groups. Logistic regression demonstrated that the LC emergence was independently affected by serum levels of myristic acid, palmitic acid, linoleic acid, eicosapentaenoic acid (EPA), lysophosphatidic acid (LPA) (18:1), glycolic acid, lysophosphatidylcholine (lysoPC) (22:6), and succinylacetone (R 2 = 0.837, P < 0.001). This prospective study revealed that dysregulation of various metabolism had the clinical relevance on the LC development. Moreover, myristic acid, palmitic acid, linoleic acid, EPA, LPA (18:1), glycolic acid, lysoPC (22:6), and succinylacetone were emerged as independent variables influencing the incidence of LC. The results support that the early biomarkers found in this study may useful for predicting and remedying the risk of LC.

14.
Korean Circ J ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31845553

RESUMO

Cardiovascular disease (CVD) is considered a primary driver of global mortality and is estimated to be responsible for approximately 17.9 million deaths annually. Consequently, a substantial body of research related to CVD has developed, with an emphasis on identifying strategies for the prevention and effective treatment of CVD. In this review, we critically examine the existing CVD literature, and specifically highlight the contribution of Mendelian randomization analyses in CVD research. Throughout this review, we assess the extent to which research findings agree across a range of studies of differing design within a triangulation framework. If differing study designs are subject to non-overlapping sources of bias, consistent findings limit the extent to which results are merely an artefact of study design. Consequently, broad agreement across differing studies can be viewed as providing more robust causal evidence in contrast to limiting the scope of the review to a single specific study design. Utilising the triangulation approach, we highlight emerging patterns in research findings, and explore the potential of identified risk factors as targets for precision medicine and novel interventions.

15.
BMJ Open Diabetes Res Care ; 7(1): e000859, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31875135

RESUMO

Objectives: Secondhand smoke (SHS) was known as one of the risk factors for type 2 diabetes. So far, some studies revealed the association of SHS exposure and type 2 diabetes, however, no studies to show the relationship of cumulative SHS exposure with type 2 diabetes exist. Therefore, the objectives of this study were to identify subgroups of participants who share similar trajectories in SHS exposure levels in middle age by using latent class growth modeling, and determine the independent association of these SHS exposure level trajectories with risk of incident type 2 diabetes. Methods: In Korean Genome and Epidemiology Study (2001-2014), 2079 participants aged 40 years and above who received biennially health check-up to follow-up and with available information of SHS exposure were selected. Four distinct trajectory groups (low-stable, moderate to low, moderate, and high to low) were identified for SHS exposure levels using trajectory modeling methods. Multivariable Cox proportional hazards model was used to examine the association of trajectories with risk of type 2 diabetes. Results: During 24 083.3 person-years of follow-up (mean follow-up duration, 11.6 years), 200 incident cases of type 2 diabetes and 640 incident cases of impaired fasting glucose (IFG) were identified. In multivariable Cox model, 'High to low' trajectory was significantly associated with risk of type 2 diabetes (OR 1.9; 95% CI 1.3 to 2.8) compared with 'Low-stable'. For IFG, all trajectories had significantly 30%-30% higher risk of type 2 diabetes compared with the 'Low-stable' trajectory. Conclusions: Changes in SHS exposure levels have been shown to associate with subsequent type 2 diabetes risk. Reversing high exposure level of SHS in middle-aged adulthood may still lead to worse progressions of type 2 diabetes than remaining stable exposure level.


Assuntos
Hipoglicemiantes/uso terapêutico , Adulto , Idoso , Biomarcadores/análise , Glicemia/análise , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores Sexuais
16.
Int J Cancer ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31745972

RESUMO

The association between body mass index (BMI) and noncardia gastric cancer (NCGC) risk remains controversial. The purpose of our study was to examine the association of BMI with NCGC risk with consideration of Helicobacter pylori (HP) biomarkers. This international nested case-control study, composed of 1,591 incident NCGC cases and 1,953 matched controls, was established from eight cohorts in China, Japan and Korea, where the majority of NCGCs are diagnosed worldwide. HP antibody biomarkers were measured in blood collected at cohort enrollment by multiplex serology. The NCGC risk according to baseline BMI was estimated using logistic regression to produce odds ratios (ORs) and 95% confidence intervals (CIs). We found a U-shaped association between BMI category and NCGC risk. Compared to those with reference BMI (22.6-25.0 kg/m2 ), those with lower and higher BMI had an increased NCGC risk (BMI <18.5 kg/m2 , OR = 1.56, 95% CI = 1.04-2.34; BMI >27.5 kg/m2 , OR = 1.48, 95% CI = 1.15-1.91; adjusted for age, sex and smoking). The U-shaped association was persistent among subjects with HP infection and high-risk biomarkers (HP+ CagA+: BMI <18.5 kg/m2 , OR = 1.60, 95% CI = 1.00-2.55; BMI >27.5 kg/m2 , OR = 1.59, 95% CI = 1.21-2.11; and Omp+ HP0305+: BMI <18.5 kg/m2 , OR = 1.88, 95% CI = 1.04-3.42; BMI >27.5 kg/m2 , OR = 1.70, 95% CI = 1.20-2.42, respectively). Our study provides evidence of significantly increased NCGC risk among individuals with low or high BMI, including in subjects with high-risk HP biomarkers (HP+ CagA+, Omp+ HP0305+) in the high-risk area of East Asia.

17.
Sci Rep ; 9(1): 14360, 2019 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591475

RESUMO

Differentiating between inherited renal hypouricemia and transient hypouricemic status is challenging. Here, we aimed to describe the genetic background of hypouricemia patients using whole-exome sequencing (WES) and assess the feasibility for genetic diagnosis using two founder variants in primary screening. We selected all cases (N = 31) with extreme hypouricemia (<1.3 mg/dl) from a Korean urban cohort of 179,381 subjects without underlying conditions. WES and corresponding downstream analyses were performed for the discovery of rare causal variants for hypouricemia. Two known recessive variants within SLC22A12 (p.Trp258*, pArg90His) were identified in 24 out of 31 subjects (77.4%). In an independent cohort, we identified 50 individuals with hypouricemia and genotyped the p.Trp258* and p.Arg90His variants; 47 of the 50 (94%) hypouricemia cases were explained by only two mutations. Four novel coding variants in SLC22A12, p.Asn136Lys, p.Thr225Lys, p.Arg284Gln, and p.Glu429Lys, were additionally identified. In silico studies predict these as pathogenic variants. This is the first study to show the value of genetic diagnostic screening for hypouricemia in the clinical setting. Screening of just two ethnic-specific variants (p.Trp258* and p.Arg90His) identified 87.7% (71/81) of Korean patients with monogenic hypouricemia. Early genetic identification of constitutive hypouricemia may prevent acute kidney injury by avoidance of dehydration and excessive exercise.

18.
Chemosphere ; 237: 124469, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31549635

RESUMO

High exposure to bisphenol A (BPA) in children has been associated with the outcomes of several diseases, including those related to developmental problems. To elucidate the mechanism of BPA mediated developmental toxicity, plasma and urine from rats exposed to BPA was analyzed with high resolution metabolomics, beginning from post-natal day 9, for 91 days. Female and male rats were orally administered 5 different BPA doses to elucidate dose- and sex-specific BPA effects. Regarding dose-specific effects, multivariate statistical analysis showed that metabolic shifts were considerably altered between 5, 50 and 250 mg BPA/kg bw/day in treated rats. A nonmonotonicity and monotonicity between BPA dose and metabolic response were major trajectories, showing overall metabolic changes in plasma and urine, respectively. Metabolic perturbation in the steroid hormone biosynthesis pathway was significantly associated with dose- and sex-specific BPA effects. Intermediate metabolites in the rate-limiting step of steroid hormone biosynthesis down-regulated steroid hormones in the 250 mg treatment. Further, our study identified that BPA increased urinary excretion of vitamin D3 and decreased its concentration in blood, suggesting that perturbation of vitamin D3 metabolism may be mechanistically associated with neurodevelopmental disorders caused by BPA. Three metabolites showed a decrease in sex difference with high BPA dose because female rats were more affected than males, which can be related with early puberty onset in female. In brief, the results demonstrated that BPA induces dose- and sex-specific metabolic shifts and that perturbation of metabolism can explain developmental problems.


Assuntos
Compostos Benzidrílicos/toxicidade , Colecalciferol/metabolismo , Disruptores Endócrinos/toxicidade , Fenóis/toxicidade , Esteroides/metabolismo , Animais , Criança , Feminino , Hormônios , Humanos , Metabolismo dos Lipídeos , Masculino , Metabolômica , Ratos , Caracteres Sexuais
19.
J Dermatol ; 46(10): 859-866, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432567

RESUMO

The association between psoriasis and risk of atherosclerotic cardiovascular disease has not been thoroughly evaluated in a large longitudinal cohort of an Asian population. We conducted a nationwide population-based retrospective cohort study encompassing more than 1.7 million Koreans with a 15-year follow-up period. The period prevalence of psoriasis was 0.33% among the baseline participants (1997-2000). In Cox proportional hazard analyses, the individuals with psoriasis had a higher adjusted hazard ratio (HR) for incidence of overall atherosclerotic cardiovascular disease (HR, 1.18; 95% confidence interval [CI], 1.09-1.27) compared with controls. Subgroup analyses revealed that the risk for myocardial infarction was commonly increased in both sexes with moderate to severe psoriasis (male: HR, 2.09; 95% CI, 1.35-3.24; female: HR, 3.23; 95% CI, 1.34-7.76), whereas the risk for ischemic stroke was specifically increased in female individuals with moderate to severe psoriasis (HR, 2.02; 95% CI, 1.24-3.30). Our data suggest that appropriate medical screening for possible cardiovascular comorbidities is warranted in Asian psoriatic patients according to disease severity and sex.


Assuntos
Angina Pectoris/epidemiologia , Aterosclerose/epidemiologia , Infarto do Miocárdio/epidemiologia , Psoríase/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Adulto , Comorbidade , Feminino , Seguimentos , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Modelos de Riscos Proporcionais , Psoríase/diagnóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais
20.
Glob Health Promot ; : 1757975919854301, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375056

RESUMO

The goal of this study was to develop a Korean version of the Global Physical Activity Questionnaire (K-GPAQ) and to examine its reliability and validity. The English version of the GPAQ was translated to the Korean language (K-GPAQ) via forward-backward translation. Reliability of the K-GPAQ was evaluated using a one-week interval test-retest method with 115 individuals. Criterion-related validity of the K-GPAQ was examined with 199 participants using accelerometers. Cohen's kappa and Spearman's correlation coefficients were used to measure test-retest reliability and validity, respectively. A Bland-Altman analysis was used to assess agreement between physical activity (PA) levels measured via K-GPAQ and the accelerometer. Coefficients for the reliability of the K-GPAQ showed moderate agreement for recreational PA and slight agreement for work-related PA (Cohen's kappa: 0.60-0.67 for recreational PA and 0.30-0.38 for work-related PA and Spearman's rho: 0.27-0.47 for work-related PA and 0.53-0.70 for recreational PA). Criterion validity of the total amount of PA, as measured by the K-GPAQ and the accelerometer, showed a weak but significant correlation (r = 0.34, p < 0.01). The K-GPAQ is a reliable and valid questionnaire to measure PA although K-GPAQ overestimated PA levels.

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