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1.
Artigo em Inglês | MEDLINE | ID: mdl-34501776

RESUMO

The evidence for the association between diurnal temperature range (DTR) and diabetic foot amputations is limited. We aimed to investigate the region-specific association between DTR and the amputation rate of diabetic foot in Korean national-wide data. Daily data on DTR and the rate of diabetic foot amputations from 16 provincial capital cities in Korea were obtained (2011-2018). In this study, the latitude ranged from 33°11' N to 38°61' N, and we classified each region according to latitude. Region 1, which was located at a relatively high latitude, included Seoul, Incheon, Gyeonggi-do, and Gangwon-do. Region 2, which was located at a relatively low latitude, included Busan, Ulsan, Gyeonsannam-do, Gwangju, Jeollanam-do, Jeollabuk-do, and Jeju-do. The region-specific DTR effects on the amputation rate were estimated based on a quasi-Poisson generalized linear model, combined with a distributed lag non-linear model based on the self-controlled case series design. The DTR impacts were generally limited to a period of nine days, while significant effects during lag days 7-14 were only found in the cities of Seoul, Incheon, and Gyeonggi-do (10th lag day: RR [95% CI]; Seoul: 1.015, [1.001-1.029]; Incheon: 1.052 [1.006-1.101]; Gyeonggi-do: 1.018 [1.002-1.034]). In the subgroup analysis (according to the latitude), an increase of 1 °C in DTR was associated with the risk of diabetic foot in relatively high latitude regions. DTR has considerable effects on the risk of diabetic foot amputation in various provinces in Korea, and it was particularly affected by latitude. The results can inform the decisions on developing programs to protect vulnerable subpopulations from adverse impacts.

2.
Environ Res ; 204(Pt B): 112093, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34562483

RESUMO

Mercury (Hg) is a ubiquitous heavy metal that originates from both natural and anthropogenic sources and is transformed in the environment to its most toxicant form, methylmercury (MeHg). Recent studies suggest that MeHg exposure can alter epigenetic modifications during embryogenesis. In this study, we examined associations between prenatal MeHg exposure and levels of cord blood DNA methylation (DNAm) by meta-analysis in up to seven independent studies (n = 1462) as well as persistence of those relationships in blood from 7 to 8 year-old children (n = 794). In cord blood, we found limited evidence of differential DNAm at cg24184221 in MED31 (ß = 2.28 × 10-4, p-value = 5.87 × 10-5) in relation to prenatal MeHg exposure. In child blood, we identified differential DNAm at cg15288800 (ß = 0.004, p-value = 4.97 × 10-5), also located in MED31. This repeated link to MED31, a gene involved in lipid metabolism and RNA Polymerase II transcription function, may suggest a DNAm perturbation related to MeHg exposure that persists into early childhood. Further, we found evidence for association between prenatal MeHg exposure and child blood DNAm levels at two additional CpGs: cg12204245 (ß = 0.002, p-value = 4.81 × 10-7) in GRK1 and cg02212000 (ß = -0.001, p-value = 8.13 × 10-7) in GGH. Prenatal MeHg exposure was associated with DNAm modifications that may influence health outcomes, such as cognitive or anthropometric development, in different populations.

5.
BMC Musculoskelet Disord ; 22(1): 565, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34154538

RESUMO

BACKGROUND: This study investigated whether achieving a higher degree of knee flexion after TKA promoted the ability to perform high-flexion activities, as well as patient satisfaction and quality of life. METHODS: Clinical data on 912 consecutive primary TKA cases involving a single high-flexion posterior stabilized fixed-bearing prosthesis were retrospectively analyzed. Demographic and clinical data were collected, including knee flexion angle, the ability to perform high-flexion activities, and patient satisfaction and quality of life. RESULTS: Of the cases, 619 (68%) achieved > 130° of knee flexion after TKA (high flexion group). Knee flexion angle and clinical scores showed significant annual changes, with the maximum improvement seen at 5 years and slight deterioration observed at 10 years postoperatively. In the high flexion group, more than 50% of the patients could not kneel or squat, and 35% could not stand up from on the floor. Multivariate analysis revealed that > 130° of knee flexion, the ability to perform high-flexion activities (sitting cross-legged and standing up from the floor), male gender, and bilateral TKA were significantly associated with patient satisfaction after TKA, while the ability to perform high-flexion activities (sitting cross-legged and standing up from the floor), male gender, and bilateral TKA were significantly associated with patient quality of life after TKA. CONCLUSIONS: High knee flexion angle (> 130°) after TKA increased the ease of high-flexion activities and patient satisfaction. The ease of high-flexion activities also increased quality of life after TKA in our Asian patients, who frequently engage in these activities in daily life.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Humanos , Articulação do Joelho/cirurgia , Masculino , Osteoartrite do Joelho/cirurgia , Satisfação do Paciente , Qualidade de Vida , Amplitude de Movimento Articular , Estudos Retrospectivos
7.
Korean J Intern Med ; 36(3): 617-628, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33858123

RESUMO

BACKGROUND/AIMS: Although it is near concluded that renin-angiotensin system inhibitors do not have a harmful effect on coronavirus disease 2019 (COVID-19), there is no report about whether angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) offer any protective role. This study aimed to compare the association of ARBs and ACEIs with COVID-19-related mortality. METHODS: All patients with COVID-19 in Korea between January 19 and April 16, 2020 were enrolled. The association of ARBs and ACEIs with mortality within 60 days were evaluated. A comparison of hazard ratio (HR) was performed between COVID-19 patients and a retrospective cohort of pneumonia patients hospitalized in 2019 in Korea. RESULTS: Among 10,448 COVID-19 patients, ARBs and ACEIs were prescribed in 1,231 (11.7%) and 57 (0.6%) patients, respectively. After adjusting for age, sex, and history of comorbidities, the ARB group showed neutral association (HR, 1.034; 95% CI, 0.765 to 1.399; p = 0.8270) and the ACEI groups showed no significant associations likely owing to the small population size (HR, 0.736; 95% CI, 0.314 to 1.726; p = 0.4810). When comparing HR between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia in 2019, the trend of ACEIs showed similar benefits, whereas the protective effect of ARBs observed in the retrospective cohort was absent in COVID-19 patients. Meta-analyses showed significant positive correlation with survival of ACEIs, whereas a neutral association between ARBs and mortality. CONCLUSION: Although ARBs or ACEIs were not associated with fatal outcomes, potential beneficial effects of ARBs observed in pneumonia were attenuated in COVID-19.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , COVID-19/diagnóstico , COVID-19/mortalidade , Hipertensão/tratamento farmacológico , Pneumonia Viral/mortalidade , Pneumonia/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , COVID-19/tratamento farmacológico , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Hipertensão/complicações , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico , Pneumonia Viral/complicações , Sistema Renina-Angiotensina , República da Coreia/epidemiologia , Estudos Retrospectivos , SARS-CoV-2 , Adulto Jovem
8.
PLoS One ; 16(4): e0249688, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33831071

RESUMO

Chronic rhinosinusitis (CRS) is characterized according to the presence or absence of nasal polyps (NPs) and displays nasal microbiota dysbiosis. However, optimal sampling methods of the nasal microbiome in CRS have not been identified. We aimed to assess the microbial composition in patients with CRS, comparing different sampling methods (swab and tissue biopsy), tissue types (uncinate tissue and NP), and disease subtypes. Samples were obtained by swabbing the middle meatus and taking a biopsy of uncinate tissue (UT) in patients with CRS with (CRSwNP, N = 8) or without NP (CRSsNP, N = 6) and controls (N = 8). NPs were also harvested in CRSwNP. DNAs were extracted from fifty-two samples and analyzed by 16S rRNA gene amplicon sequencing. As a result, a great interpersonal variance was observed in nasal swabs, while UT samples presented distinct microbiome with low inter-personal differences. Moreover, the UT microbiomes were further differentiated into three clusters which are associated with disease status (control, CRSsNP, and CRSwNP). Compared to UT, NP revealed a unique microbiome profile with significantly less bacterial diversity. Prevotella was the genus whose abundance was negatively correlated with disease severity in NP. In conclusion, tissue samples are better specimens than nasal swabs for assessing the microbiomes of CRS patients. Several bacteria in UT and NP tissues revealed an association with clinical severity of CRSwNP.


Assuntos
Bactérias/genética , Microbiota/genética , Pólipos Nasais/microbiologia , Sinusite/microbiologia , Adulto , Biópsia/métodos , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Manejo de Espécimes/métodos
9.
Thorax ; 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888571

RESUMO

Most genome-wide association studies of obesity and body mass index (BMI) have so far assumed an additive mode of inheritance in their analysis, although association testing supports a recessive effect for some of the established loci, for example, rs1421085 in FTO In two whole-genome sequencing (WGS) studies of children with asthma and their parents (892 Costa Rican trios and 286 North American trios), we discovered an association between a locus (rs9292139) in LOC102724122 and BMI that reaches genome-wide significance under a recessive model in the combined analysis. As the association does not achieve significance under an additive model, our finding illustrates the benefits of the recessive model in WGS analyses.

10.
Sci Rep ; 11(1): 5001, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33654129

RESUMO

Multiple environmental factors could interact with a single genetic factor to affect disease phenotypes. We used Struct-LMM to identify genetic variants that interacted with environmental factors related to body mass index (BMI) using data from the Korea Association Resource. The following factors were investigated: alcohol consumption, education, physical activity metabolic equivalent of task (PAMET), income, total calorie intake, protein intake, carbohydrate intake, and smoking status. Initial analysis identified 7 potential single nucleotide polymorphisms (SNPs) that interacted with the environmental factors (P value < 5.00 × 10-6). Of the 8 environmental factors, PAMET score was excluded for further analysis since it had an average Bayes Factor (BF) value < 1 (BF = 0.88). Interaction analysis using 7 environmental factors identified 11 SNPs (P value < 5.00 × 10-6). Of these, rs2391331 had the most significant interaction (P value = 7.27 × 10-9) and was located within the intron of EFNB2 (Chr 13). In addition, the gene-based genome-wide association study verified EFNB2 gene significantly interacting with 7 environmental factors (P value = 5.03 × 10-10). BF analysis indicated that most environmental factors, except carbohydrate intake, contributed to the interaction of rs2391331 on BMI. Although the replication of the results in other cohorts is warranted, these findings proved the usefulness of Struct-LMM to identify the gene-environment interaction affecting disease.

11.
Arterioscler Thromb Vasc Biol ; 41(3): e175-e182, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33535790

RESUMO

OBJECTIVE: Although statins are widely prescribed lipid-lowering drugs, there are concerns about the safety of their use in the context of coronavirus disease 2019 (COVID-19), since statins increase the expression of ACE2 (angiotensin-converting enzyme 2). This study aimed to disclose the association between statins and 60-day COVID-19 mortality. Approach and Results: All patients hospitalized with laboratory-confirmed COVID-19 were enrolled in this study from January 19 to April 16, 2020, in Korea. We evaluated the association between the use of statins and COVID-19-related mortality in the overall and the nested 1:2 propensity score-matched study. Furthermore, a comparison of the hazard ratio for death was performed between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia between January and June 2019 in Korea. The median age of the 10 448 COVID-19 patients was 45 years. Statins were prescribed in 533 (5.1%) patients. After adjusting for age, sex, and comorbidities, Cox regression showed a significant decrease in hazard ratio associated with the use of statins (hazard ratio, 0.637 [95% CI, 0.425-0.953]; P=0.0283). Moreover, on comparing the hazard ratio between COVID-19 patients and the retrospective cohort of hospitalized pneumonia patients, the use of statins showed similar benefits. CONCLUSIONS: The use of statins correlates significantly with lower mortality in patients with COVID-19, consistent with the findings in patients with pneumonia. Graphic Abstract: A graphic abstract is available for this article.


Assuntos
COVID-19/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pandemias , SARS-CoV-2 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , COVID-19/mortalidade , Criança , Pré-Escolar , Estudos de Coortes , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/mortalidade , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/mortalidade , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Pneumonia/tratamento farmacológico , Pneumonia/mortalidade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/mortalidade , República da Coreia/epidemiologia , Estudos Retrospectivos , Adulto Jovem
12.
Sci Rep ; 11(1): 1442, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446854

RESUMO

Medical costs have recently increased in South Korea due to the rising rate of asthma. Primary clinics serve an important role in asthma management, as they are the first stop for patients presenting with symptoms. The Health Insurance Review and Assessment Service (HIRA) in South Korea has assessed asthma-management quality since 2013, but studies are lacking on whether these assessments have been performed properly and contribute toward reducing asthma exacerbations. Therefore, we investigated whether the HIRA's quality assessments have decreased asthma exacerbations using national health insurance claims data from 2013 to 2017 of 83,375 primary-clinic and 15,931 tertiary-hospital patients with asthma. These patients were classified into four groups based on disease severity according to the monthly prescribed amount of asthma medication using K-means clustering. The associations between HIRA assessments and asthma exacerbation were analyzed using a generalized estimating equation. Our results showed that exacerbation odds gradually decreased as the HIRA assessments progressed, especially in the mild-severity group, and that exacerbation risk among patients with asthma decreased in the order of assessment grades: "Unsatisfactory," "Satisfactory," and "Tertiary." Therefore, we may conclude that asthma exacerbations may decrease with high quality asthma management; appropriate quality assessment could be helpful in reducing asthma exacerbations.


Assuntos
Asma , Atenção à Saúde , Hospitalização , Revisão da Utilização de Seguros , Programas Nacionais de Saúde , Adolescente , Adulto , Idoso , Asma/epidemiologia , Asma/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Retrospectivos , Índice de Gravidade de Doença
13.
Environ Res ; 195: 110767, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33515580

RESUMO

BACKGROUND: Prenatal lead exposure has been reported to affect infant growth and nervous system development, as well as to influence DNA methylation. We conducted an epigenome-wide association study to identify associations between prenatal lead exposure and cord blood DNA methylation in Korean infants. METHODS: Cord blood samples were assayed with the Illumina HumanMethylationEPIC BeadChip kits, and maternal blood lead levels during early and late pregnancy, as well as cord blood lead level, were measured. The association between CpG methylation and lead level was analyzed using the limma package, with adjusting for infant sex, maternal pre-pregnancy body mass index, and estimated leukocyte composition. RESULTS: Among 364 blood samples (182 males and 182 females), those for which maternal and cord blood lead concentrations during early and later pregnancy was known were used for analysis. Maternal lead concentration in blood during early pregnancy was significantly associated with the methylation status of specific positions. After data stratification by infant sex, we found that, in males, the level of maternal blood lead was associated with 18 CpG sites during early pregnancy, and with one CpG site near the NBAS gene, during late pregnancy. In female samples, there was no significant association between DNA methylation and lead concentrations. CONCLUSIONS: Prenatal lead exposure was associated with altered, gender-specific patterns of DNA methylation in Korean infants.


Assuntos
Expossoma , Efeitos Tardios da Exposição Pré-Natal , Ilhas de CpG , Metilação de DNA , Feminino , Sangue Fetal/metabolismo , Humanos , Lactente , Chumbo/metabolismo , Chumbo/toxicidade , Masculino , Exposição Materna/efeitos adversos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , República da Coreia
14.
Nat Microbiol ; 6(3): 277-288, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33432149

RESUMO

The gut microbiome can influence the development of tumours and the efficacy of cancer therapeutics1-5; however, the multi-omics characteristics of antitumour bacterial strains have not been fully elucidated. In this study, we integrated metagenomics, genomics and transcriptomics of bacteria, and analyses of mouse intestinal transcriptome and serum metabolome data to reveal an additional mechanism by which bacteria determine the efficacy of cancer therapeutics. In gut microbiome analyses of 96 samples from patients with non-small-cell lung cancer, Bifidobacterium bifidum was abundant in patients responsive to therapy. However, when we treated syngeneic mouse tumours with commercial strains of B. bifidum to establish relevance for potential therapeutic uses, only specific B. bifidum strains reduced tumour burden synergistically with PD-1 blockade or oxaliplatin treatment by eliciting an antitumour host immune response. In mice, these strains induced tuning of the immunological background by potentiating the production of interferon-γ, probably through the enhanced biosynthesis of immune-stimulating molecules and metabolites.


Assuntos
Bifidobacterium bifidum/fisiologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Probióticos/uso terapêutico , Carga Tumoral/efeitos dos fármacos , Animais , Bifidobacterium bifidum/classificação , Bifidobacterium bifidum/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/microbiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimioterapia Combinada , Microbioma Gastrointestinal , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/microbiologia , Neoplasias Pulmonares/patologia , Metaboloma/efeitos dos fármacos , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Probióticos/administração & dosagem , Especificidade da Espécie , Transcriptoma/efeitos dos fármacos , Triptofano/metabolismo
15.
J Allergy Clin Immunol ; 147(4): 1453-1463, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32795589

RESUMO

BACKGROUND: The relationship between allergic and eosinophilic inflammation, either systemic or local, in allergic diseases remains unclear. OBJECTIVE: We performed combined genome-wide association study (GWAS) and epigenome-wide (EWAS) for atopy and tissue eosinophilia to identify both genetic and epigenetic signatures between systemic and local allergic inflammation, and to capture global patterns of gene regulation. METHODS: We included 126 subjects for atopy analysis and 147 for tissue eosinophilia analysis, as well as 18 normal nasal tissue samples. We identified differentially methylated positions (DMPs) and genes associated with atopy and tissue eosinophilia. Furthermore, we performed mendelian randomization analysis and penalized regression along with replication in an independent cohort. RESULTS: EWAS identified genes, including Musashi RNA binding protein 2 (MSI2), associated with atopy, which contained enriched DMPs that genetically affect atopy. A direct association was observed between MSI2 single-nucleotide polymorphisms and atopy, as was a causal effect of changes in MSI2 expression and methylation on atopy, which was replicated in a Costa Rican population. Regarding tissue eosinophilia, EWAS identified genes with enriched DMPs directly contributing to tissue eosinophilia at the gene level, including CAMK1D. The gene ontology terms of the identified genes for both phenotypes encompassed immune-related terms. CONCLUSION: EWAS combined with GWAS identified novel candidate genes, especially the methylation of MSI2, contributing to systemic allergic inflammation. Certain genes displayed a greater association with either systemic or local allergic inflammation; however, it is expected that a harmonized effect of these genes influences immune responses.

17.
Eur Respir J ; 57(2)2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32855217

RESUMO

Most children diagnosed with asthma have respiratory symptoms such as cough, dyspnoea and wheezing, which are also important markers of overall respiratory function. A decade of genome-wide association studies (GWAS) have investigated genetic susceptibility to asthma itself, but few have focused on important respiratory symptoms that characterise childhood asthma.Using whole-genome sequencing (WGS) data for 894 asthmatic trios from a Costa Rican cohort, we performed family-based association tests (FBATs) to assess the association between genetic variants and multiple asthma-relevant respiratory phenotypes: cough, phlegm, wheezing, exertional dyspnoea and exertional chest tightness. We tested whether genome-wide significant associations were replicated in two additional studies: 1) 286 asthmatic trios from the Childhood Asthma Management Program (CAMP), and 2) 2691 African American current or former smokers from the COPDGene study.In the 894 Costa Rican trios, we identified a genome-wide significant association (p=2.16×10-9) between exertional dyspnoea and the single nucleotide polymorphism (SNP) rs10165869, located on chromosome 2q37.3, that was replicated in the CAMP cohort (p=0.023) with the same direction of association (combined p=3.28×10-10). This association was not found in the African American participants from COPDGene. We also found suggestive evidence for an association between SNP rs10165869 and the atypical chemokine receptor 3 (ACKR3).Our finding encourages the secondary association analysis of a wider range of phenotypes that characterise respiratory symptoms in other airway diseases/studies.

18.
Thorax ; 76(2): 169-177, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33115937

RESUMO

BACKGROUND: The prevalence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing in South Korea and many parts of the world. However, the genetic factors underlying susceptibility to this disease remain elusive. METHODS: To identify genetic variants in patients with NTM-PD, we performed a genome-wide association study with 403 Korean patients with NTM-PD and 306 healthy controls from the Healthy Twin Study, Korea cohort. Candidate variants from the discovery cohort were subsequently validated in an independent cohort. The Genotype-Tissue Expression (GTEx) database was used to identify expression quantitative trait loci (eQTL) and to conduct Mendelian randomisation (MR). RESULTS: We identified a putatively significant locus on chromosome 7p13, rs849177 (OR, 2.34; 95% CI, 1.71 to 3.21; p=1.36×10-7), as the candidate genetic variant associated with NTM-PD susceptibility. Its association was subsequently replicated and the combined p value was 4.92×10-8. The eQTL analysis showed that a risk allele at rs849177 was associated with lower expression levels of STK17A, a proapoptotic gene. In the MR analysis, a causal effect of STK17A on NTM-PD development was identified (ß, -4.627; 95% CI, -8.768 to -0.486; p=0.029). CONCLUSIONS: The 7p13 genetic variant might be associated with susceptibility to NTM-PD in the Korean population by altering the expression level of STK17A.

19.
Lifestyle Genom ; 14(1): 20-29, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33302275

RESUMO

INTRODUCTION: Obesity results from an imbalance in the intake and expenditure of calories that leads to lifestyle-related diseases. Although genome-wide association studies (GWAS) have revealed many obesity-related genetic factors, the interactions of these factors and calorie intake remain unknown. This study aimed to investigate interactions between calorie intake and the polygenic risk score (PRS) of BMI. METHODS: Three cohorts, i.e., from the Korea Association REsource (KARE; n = 8,736), CArdioVAscular Disease Association Study (CAVAS; n = 9,334), and Health EXAminee (HEXA; n = 28,445), were used for this study. BMI-related genetic loci were selected from previous GWAS. Two scores, PRS, and association (a)PRS, were used; the former was determined from 193 single-nucleotide polymorphisms (SNPs) from 5 GWAS datasets, and the latter from 62 SNPs (potentially associated) from 3 Korean cohorts (meta-analysis, p < 0.01). RESULTS: PRS and aPRS were significantly associated with BMI in all 3 cohorts but did not exhibit a significant interaction with total calorie intake. Similar results were obtained for obesity. PRS and aPRS were significantly associated with obesity but did not show a significant interaction with total calorie intake. We further analyzed the interaction with protein, fat, and carbohydrate intake. The results were similar to those for total calorie intake, with PRS and aPRS found to not be associated with the interaction of any of the 3 nutrition components for either BMI or obesity. DISCUSSION: The interaction of BMI PRS with calorie intake was investigated in 3 independent Korean cohorts (total n = 35,094) and no interactions were found between PRS and calorie intake for obesity.

20.
J Transl Med ; 18(1): 464, 2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-33287847

RESUMO

BACKGROUND: Healthcare-associated pneumonia (HCAP) is a heterogeneous disease. We redefined nursing-home- and hospital-associated infections (NHAI) group by revising existing HCAP risk factors. The NHAI group comprised nursing home residents with a poor functional status, or recent (past 90 days) hospitalization or recent (past 180 days) antibiotic therapy. Our aim was to determine whether respiratory microbiota profiles are related to newly defined NHAI group in critically ill patients on mechanical ventilation. METHODS: The 180 endotracheal aspirates (ETAs) from 60 mechanically ventilated ICU patients (NHAI group, n = 24; non-NHAI group, n = 36) were prospectively collected on days 1, 3 and 7 in a university hospital. The bacterial community profiles of the ETAs were explored by 16S rRNA gene sequencing. A phylogenetic-tree-based microbiome association test (TMAT), generalized linear mixed models (GLMMs), the Wilcoxon test and the reference frame method were used to analyze the association between microbiome abundance and disease phenotype. RESULTS: The relative abundance of the genus Corynebacterium was significantly higher in the pneumonia than in the non-pneumonia group. The microbiome analysis revealed significantly lower α-diversity in the NHAI group than in the non-NHAI group. In the analysis of ß-diversity, the structure of the microbiome also differed significantly between the two groups (weighted UniFrac distance, Adonis, p < 0.001). The abundance of Corynebacterium was significantly higher, and the relative abundances of Granulicatella, Staphylococcus, Streptococcus and Veillonella were significantly lower, in the NHAI group than in the non-NHAI group. CONCLUSIONS: The microbiota signature of the ETAs distinguished between patients with and without risk factors for NHAI. The lung microbiome may serve as a therapeutic target for NHAI group.


Assuntos
Microbiota , Respiração Artificial , Hospitalização , Humanos , Casas de Saúde , Filogenia , RNA Ribossômico 16S/genética
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