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BACKGROUND: We aimed to probe the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with all-cause and cause-specific mortality among patients with gout and hyperuricemia (HUA). METHODS: The study included 1169 gout patients and 7029 HUA patients from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 and 2001-2018, respectively. The association between serum 25(OH)D and mortality was evaluated by Cox proportional hazard and restricted cubic spline models. RESULTS: Among participants with gout and HUA, the weighted mean concentrations of serum 25(OH)D were 71.49 ± 30.09 nmol/L and 64.81 ± 26.92 nmol/L, respectively. Vitamin D deficiency occurred in 29.68% of gout patients and 37.83% of HUA patients. During 6783 person-years of follow-up among gout patients, 248 all-cause deaths occurred, among which 76 died from cardiovascular disease (CVD) and 49 died from cancer. 1375 HUA patients were recorded for all-cause mortality during 59,859 person-years of follow-up, including 427 CVD deaths and 232 cancer deaths. After multifactorial adjustment, per one-unit increment in natural log-transformed 25(OH)D was associated with lower risk of 55% all-cause mortality and 61% CVD mortality among gout patients, and a 45% reduced risk of cancer mortality among HUA patients. Restricted cubic splines showed a U-shaped relationship with all-cause and CVD mortality among HUA patients, with inflection points of 72.7 nmol/L and 38.0 nmol/L, respectively. The results were robust in subgroup and sensitivity analyses. CONCLUSIONS: Serum 25(OH)D was negatively linearly correlated with mortality among gout patients, whereas U-shaped correlated with mortality in HUA patients. These results indicate that adequate vitamin D status could prevent premature death.
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Causas de Morte , Gota , Hiperuricemia , Inquéritos Nutricionais , Vitamina D , Humanos , Gota/sangue , Gota/mortalidade , Gota/complicações , Hiperuricemia/sangue , Hiperuricemia/mortalidade , Hiperuricemia/complicações , Vitamina D/análogos & derivados , Vitamina D/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Inquéritos Nutricionais/estatística & dados numéricos , Adulto , Idoso , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangue , Neoplasias/mortalidade , Neoplasias/sangue , Neoplasias/complicações , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/mortalidade , Modelos de Riscos ProporcionaisRESUMO
Background: Modifiable factors were found to be associated with the risk of irritable bowel syndrome (IBS) in observational studies, but whether these associations are causal is uncertain. We conducted a Mendelian randomization (MR) study to systematically explore the causal associations of modifiable factors with IBS. Methods: Summary-level statistical data for IBS was obtained from a genome-wide association study (GWAS) meta-analysis of UK Biobank (40,548 cases and 293,220 controls) and the international collaborative Bellygenes initiative (12,852 cases and 139,981 controls). Genetic instruments associated with the exposures at the genome-wide significance (p < 5 × 10-8) level were selected from previous GWASs. Mendelian randomization was performed using inverse-variance weighted (IVW) method, supplemented with several sensitivity analyses to evaluate potentially causal relationships between identified contributing factors and IBS. Furthermore, we applied another database from FinnGen (8,116 IBS cases and 276,683 controls) to testify the reliability of the significant associations. Results: Seven convincing modifiable factors were significantly associated with IBS after correction for multiple testing. Genetically predicted smoking initiation (OR = 1.12, 95% CI = 1.06-1.18, p = 1.03 × 10-4), alcohol consumption (OR = 0.47, 95% CI = 0.34-0.64, p = 3.49 × 10-6), sedentary behavior (OR = 1.17, 95% CI = 1.07-1.28, p = 4.02 × 10-4), chronotype (OR = 0.92, 95% CI = 0.88-0.96, p = 4.42 × 10-4), insomnia (OR = 1.19, 95% CI = 1.15-1.24, p = 7.59 × 10-19), education (OR = 0.80, 95% CI = 0.74-0.88, p = 5.34 × 10-7), and visceral adiposity (OR = 1.15, 95% CI = 1.06-1.24, p = 7.96 × 10-4). We additionally identified several suggestive factors, including serum magnesium, serum phosphorus, physical activity, lifetime smoking, intelligence, lean body mass, and body mass index (BMI). After pooling the effect estimates from FinnGen, the associations remained significant except for chronotype. Conclusion: This MR analysis verified several modifiable risk factors for IBS, thus prevention strategies for IBS should be considered from multiple perspectives on these risk factors.
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BACKGROUND: The investigation of dietary micronutrient intakes and risk of alcoholic liver disease (ALD) based on observational studies was limited. OBJECTIVES: Our study aimed to explore the associations of 30 dietary micronutrients intakes with risk of ALD, interactions between dietary micronutrients and genetic variation, and mediation effects of blood and urinary biomarkers on the associations between dietary micronutrients and risk of ALD. METHODS: A case-control study was conducted within the UK Biobank cohort, with 231 incident ALD cases and 1386 controls. Dietary data were collected using a dietary questionnaire that relied on a 24-h dietary recall of the previous day. Logistic regression models were employed to assess the associations of dietary micronutrient intakes with risk of ALD. We conducted stratified analyses on the associations between dietary micronutrient intakes and risk of ALD by PNPLA3 rs738409 and tested the interactions between dietary micronutrients and genetic variation. In addition, we conducted mediation analyses to investigate the mediating effects of biomarkers on the associations between dietary micronutrients and risk of ALD. RESULTS: Our findings indicated significant inverse associations of thiamin, riboflavin, niacin equivalent, pantothenic acid, vitamin B-6, folate, vitamin E, calcium, magnesium, phosphorus, potassium, copper, iodine, and manganese with risk of ALD (all false discovery rate-Ptrend < 0.050). We also found a significant interaction between PNPLA3 rs738409 and magnesium (Pinteraction = 0.028). Creatinine (enzymatic) in urine, aspartate aminotransferase, and insulin-like growth factor 1 were the top 3 biomarkers with the highest number of significant mediation effects on the associations between the dietary micronutrients and risk of ALD. CONCLUSIONS: Dietary intakes of thiamin, riboflavin, niacin equivalent, pantothenic acid, vitamin B-6, folate, vitamin E, calcium, magnesium, phosphorus, potassium, copper, iodine, and manganese were inversely associated with risk of ALD.
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The emergence of various variants of concern (VOCs) necessitates the development of more efficient vaccines for COVID-19. In this study, we established a rapid and robust production platform for a novel subunit vaccine candidate based on eukaryotic HEK-293 T cells. The immunogenicity of the vaccine candidate was evaluated in pigs. The results demonstrated that the pseudovirus neutralizing antibody (pNAb) titers reached 7751 and 306 for the SARS-CoV-2 Delta and Omicron variants, respectively, after the first boost. Subsequently, pNAb titers further increased to 10,201 and 1350, respectively, after the second boost. Additionally, ELISPOT analysis revealed a robust T-cell response characterized by IFN-γ (171 SFCs/106 cells) and IL-2 (101 SFCs/106 cells) production. Our study demonstrates that a vaccine candidate based on the Delta variant spike protein may provide strong and broad protection against the prototype SARS-CoV-2 and VOCs. Moreover, the strategy for the efficient and stable expression of recombinant proteins utilizing HEK-293 T cells can be employed as a universal platform for future vaccine development.
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Anticorpos Neutralizantes , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vacinas de Subunidades Antigênicas , Animais , Humanos , Células HEK293 , Vacinas contra COVID-19/imunologia , Vacinas de Subunidades Antigênicas/imunologia , SARS-CoV-2/imunologia , Anticorpos Neutralizantes/imunologia , Suínos , COVID-19/prevenção & controle , COVID-19/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Anticorpos Antivirais/imunologia , Linfócitos T/imunologia , Imunogenicidade da VacinaRESUMO
Irritable bowel syndrome (IBS) patients exhibit significantly lower levels of serum selenium (Se) compared to healthy controls. This study integrates a prospective cohort analysis and animal experiments to investigate Se deficiency as a potential risk factor for IBS. Using data from the UK Biobank, a longitudinal analysis was conducted to explore the associations between dietary Se intake and the risk of incident IBS. In animal study, C57BL/6 mice were fed diets with normal (0.2â¯ppm) or low (0.02â¯ppm) Se levels to assess the impacts of Se deficiency on IBS symptoms. Furthermore, we performed 16â¯S rRNA sequencing, untargeted colonic fecal metabolomics analysis, and colon transcriptome profiling to uncover the regulatory mechanisms underlying Se deficiency-induced IBS. The analysis of UK Biobank data revealed a significant correlation between low dietary Se levels and an increased incidence of IBS. In the experimental study, a low Se diet induced IBS symptoms, evidenced by elevated abdominal withdrawal reflex scores, colon inflammation, and severe pathological damage to the colon. Additionally, the low Se diet caused disturbances in gut microbiota, characterized by an increase in Faecalibaculum and Helicobacter, and a decrease in Bifidobacterium and Akkermansia. Combined colonic fecal metabolomics and colon transcriptome analysis indicated that Se deficiency might trigger IBS through disruptions in pathways related to "bile excretion", "steroid hormone biosynthesis", "arachidonic acid metabolism", and "drug metabolism-cytochrome P450". These findings underscore the significant adverse effects of Se deficiency on IBS and suggest that Se supplementation should be considered for IBS patients.
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Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Camundongos Endogâmicos C57BL , Selênio , Animais , Selênio/deficiência , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Reino Unido , Fezes/química , Masculino , Humanos , Bancos de Espécimes Biológicos , Feminino , Colo/efeitos dos fármacos , Colo/patologia , Dieta , Pessoa de Meia-Idade , Estudos Prospectivos , Biobanco do Reino UnidoRESUMO
BACKGROUND: In vitro disease modeling enables translational research by providing insight into disease pathophysiology and molecular mechanisms, leading to the development of novel therapeutics. Nevertheless, in vitro systems have limitations for recapitulating the complexity of tissues, and a single model system is insufficient to gain a comprehensive understanding of a disease. RESULTS: Here we explored the potential of using several models in combination to provide mechanistic insight into hereditary hemorrhagic telangiectasia (HHT), a genetic vascular disorder. Genome editing was performed to establish hPSCs (H9) with ENG haploinsufficiency and several in vitro models were used to recapitulate the functional aspects of the cells that constitute blood vessels. In a 2D culture system, endothelial cells showed early senescence, reduced viability, and heightened susceptibility to apoptotic insults, and smooth muscle cells (SMCs) exhibited similar behavior to their wild-type counterparts. Features of HHT were evident in 3D blood-vessel organoid systems, including thickening of capillary structures, decreased interaction between ECs and surrounding SMCs, and reduced cell viability. Features of ENG haploinsufficiency were observed in arterial and venous EC subtypes, with arterial ECs showing significant impairments. Molecular biological approaches confirmed the significant downregulation of Notch signaling in HHT-ECs. CONCLUSIONS: Overall, we demonstrated refined research strategies to enhance our comprehension of HHT, providing valuable insights for pathogenic analysis and the exploration of innovative therapeutic interventions. Additionally, these results underscore the importance of employing diverse in vitro systems to assess multiple aspects of disease, which is challenging using a single in vitro system.
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Few prospective studies have investigated the joint effect of lifestyle factors and genetic susceptibility on the risk of irritable bowel syndrome (IBS). This study aims to evaluate the associations of lifestyle and genetic factors with incident IBS in the UK Biobank. We analyzed data from 481,057 participants (54% female) without prevalent IBS at enrollment in the UK Biobank. An overall healthy lifestyle was defined using six modifiable lifestyle factors, including smoking, body mass index (BMI), sleep duration, diet, physical activity, and alcohol consumption, and hence categorized into 'favorable', 'intermediate', and 'unfavorable' lifestyles. A Cox proportional hazard model was used to investigate the association between a healthy lifestyle and incident IBS. Furthermore, we constructed a polygenic risk score (PRS) for IBS and assessed whether lifestyle modified the effect of genetics on the development of IBS. During a median follow-up of 12.1 years, 8645 incident IBS were ascertained. Specifically, among the six modifiable lifestyle factors, adequate sleep demonstrates the greatest protective effect (hazard ratio [HR]: 0.72, 95% CI: 0.69,0.75) against IBS. Compared with a favorable lifestyle, an unfavorable lifestyle was associated with a 56% (95% CI: 46%-67%) increased risk of IBS (P = 8.99 × 10-40). The risk of incident IBS was 12% (95% CI: 4%-21%) higher among those at high genetic risk compared with those at low genetic risk (P = 0.005). When considering the joint effect of lifestyle and genetic susceptibility, the HR nearly doubled among individuals with high genetic risk and unfavorable lifestyle (HR: 1.80; 95% CI:1.51-2.15; P = 3.50 × 10-11) compared to those with low genetic risk and favorable lifestyle. No multiplicative or addictive interaction was observed between lifestyle and genetics. The findings from this study indicated that lifestyle and genetic factors were independently associated with the risk of incident IBS. All these results implicated a possible clinical strategy of lowering the incidence of IBS by advocating a healthy lifestyle.
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Predisposição Genética para Doença , Síndrome do Intestino Irritável , Estilo de Vida , Humanos , Síndrome do Intestino Irritável/genética , Síndrome do Intestino Irritável/epidemiologia , Feminino , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Incidência , Reino Unido/epidemiologia , Fatores de Risco , Adulto , Modelos de Riscos Proporcionais , Idoso , Sono/genética , Estilo de Vida Saudável , Dieta/estatística & dados numéricosRESUMO
OBJECTIVE: Although previous studies have explored the association of drinking with gout risk, we sought to explore the dose-response relationship and the evidence between subtypes of alcoholic beverages and gout risk. METHODS: The weekly alcoholic beverage consumption of patients in the UK Biobank was collected and calculated. The Cox regression model was applied to assess the effects of drinking alcohol in general and its subtypes on gout risk by calculating the hazard ratio (HR) and 95% CIs. Additionally, the restricted cubic splines were used to estimate the dose-response relationship between alcohol consumption and gout risk. To evaluate the robustness, we performed subgroup analysis across various demographic characteristics. RESULTS: During a mean follow-up period of 11.7 years, a total of 5728 new incident gout cases were diagnosed among 331,865 participants. We found that light alcohol consumption was linked to a slight decrease in gout incidence among female individuals (HR 0.78, 95% CI 0.65-0.94, P = 0.01), whereas there was no significant association in male individuals. Moreover, the dose-response relationship showed that drinking light red wine and fortified wine could reduce the gout risk, whereas beer or cider, champagne or white wine, and spirits increased the gout risk at any dose. CONCLUSION: Our study suggested a J-shaped dose-response relationship between drinking and gout risk in female individuals, but not in male individuals. For specific alcoholic beverages, light consumption of red wine and fortified wine was associated with reduced gout risk. These findings offer new insights into the roles of alcoholic beverages in gout incidence risk, although further validation is warranted.
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Consumo de Bebidas Alcoólicas , Bebidas Alcoólicas , Gota , Humanos , Gota/epidemiologia , Gota/etiologia , Masculino , Feminino , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Pessoa de Meia-Idade , Bebidas Alcoólicas/efeitos adversos , Incidência , Adulto , Idoso , Reino Unido/epidemiologia , Fatores de Risco , Relação Dose-Resposta a Droga , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: Despite substantial research revealing that patients with rheumatoid arthritis (RA) have excessive morbidity and mortality of cardiovascular disease (CVD), the mechanism underlying this association has not been fully known. This study aims to systematically investigate the phenotypic and genetic correlation between RA and CVD. METHODS: Based on UK Biobank, we conducted two cohort studies to evaluate the phenotypic relationships between RA and CVD, including atrial fibrillation (AF), coronary artery disease (CAD), heart failure (HF), and stroke. Next, we used linkage disequilibrium score regression, Local Analysis of [co]Variant Association, and bivariate causal mixture model (MiXeR) methods to examine the genetic correlation and polygenic overlap between RA and CVD, using genome-wide association summary statistics. Furthermore, we explored specific shared genetic loci by conjunctional false discovery rate analysis and association analysis based on subsets. RESULTS: Compared with the general population, RA patients showed a higher incidence of CVD (hazard ratio [HR] = 1.21, 95% confidence interval [CI]: 1.15-1.28). We observed positive genetic correlations of RA with AF and stroke, and a mixture of negative and positive local genetic correlations underlying the global genetic correlation for CAD and HF, with 13 ~ 33% of shared genetic variants for these trait pairs. We further identified 23 pleiotropic loci associated with RA and at least one CVD, including one novel locus (rs7098414, TSPAN14, 10q23.1). Genes mapped to these shared loci were enriched in immune and inflammatory-related pathways, and modifiable risk factors, such as high diastolic blood pressure. CONCLUSIONS: This study revealed the shared genetic architecture of RA and CVD, which may facilitate drug target identification and improved clinical management.
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Artrite Reumatoide , Doenças Cardiovasculares , Doença da Artéria Coronariana , Insuficiência Cardíaca , Acidente Vascular Cerebral , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Estudo de Associação Genômica Ampla/métodos , Predisposição Genética para Doença/genética , Artrite Reumatoide/genética , Artrite Reumatoide/epidemiologia , Doença da Artéria Coronariana/genética , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
BACKGROUND: Limited research has been conducted on the association between long-term exposure to air pollutants and the incidence of gout. OBJECTIVES: This study aims to assess the individual and combined effects of prolonged exposure to five air pollutants (NO2, NOx, PM10, PMcoarse and PM2.52) on the incidence of gout among 458,884 initially gout-free participants enrolled in the UK Biobank. METHODS: Employing a land use regression model, we utilized an estimation method to ascertain the annual concentrations of the five air pollutants. Subsequently, we devised a weighted air pollution score to facilitate a comprehensive evaluation of exposure. The Cox proportional hazards model was utilized to investigate the association between ambient air pollution and gout risk. Interaction and stratification analyses were conducted to evaluate age, sex, BMI, and genetic predisposition as potential effect modifiers in the air pollution-gout relationship. Furthermore, mediation analyses were conducted to explore the potential involvement of biomarkers in mediating the association between air pollution and gout. RESULTS: Over a median follow-up time of 12.0 years, 7,927 cases of gout were diagnosed. Significant associations were observed between the risk of gout and a per IQR increase in NO2 (HR3: 1.05, 95 % CI4: 1.02-1.08, p = 0.003), NOx (HR: 1.04, 95 % CI: 1.01-1.06, p = 0.003), and PM2.5 (HR: 1.03, 95 % CI: 1.00-1.06, p = 0.030). Per IQR increase in the air pollution score was associated with an elevated risk of gout (p = 0.005). Stratified analysis revealed a significant correlation between the air pollution score and gout risk in participants ≥60 years (HR: 1.05, 95 % CI: 1.02-1.09, p = 0.005), but not in those <60 years (p = 0.793), indicating a significant interaction effect with age (p-interaction=0.009). Mediation analyses identified five serum biomarkers (SUA:15.87 %, VITD: 5.04 %, LDLD: 3.34 %, GGT: 1.90 %, AST: 1.56 %5) with potential mediation effects on this association. CONCLUSIONS: Long-term exposure to air pollutants, particularly among the elderly population, is associated with an increased risk of gout. The underlying mechanisms of these associations may involve the participation of five serum biomarkers.
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Poluentes Atmosféricos , Poluição do Ar , Gota , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Predisposição Genética para Doença , Gota/epidemiologia , Gota/genética , Incidência , Material Particulado/efeitos adversos , Estudos Prospectivos , Fatores de Risco , Biobanco do Reino Unido , Reino Unido/epidemiologiaRESUMO
Periodontitis drives irreversible destruction of periodontal tissue and is prone to exacerbating inflammatory disorders. Systemic immunomodulatory management continues to be an attractive approach in periodontal care, particularly within the context of 'predictive, preventive, and personalized' periodontics. The present study incorporated genetic proxies identified through genome-wide association studies for circulating immune cells and periodontitis into a comprehensive Mendelian randomization (MR) framework. Univariable MR, multivariable MR, subgroup analysis, reverse MR, and Bayesian model averaging (MR-BMA) were utilized to investigate the causal relationships. Furthermore, transcriptome-wide association study and colocalization analysis were deployed to pinpoint the underlying genes. Consequently, the MR study indicated a causal association between circulating neutrophils, natural killer T cells, plasmacytoid dendritic cells, and an elevated risk of periodontitis. MR-BMA analysis revealed that neutrophils were the primary contributors to periodontitis. The high-confidence genes S100A9 and S100A12, located on 1q21.3, could potentially serve as immunomodulatory targets for neutrophil-mediated periodontitis. These findings hold promise for early diagnosis, risk assessment, targeted prevention, and personalized treatment of periodontitis. Considering the marginal association observed in our study, further research is required to comprehend the biological underpinnings and ascertain the clinical relevance thoroughly.
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Estudo de Associação Genômica Ampla , Periodontite , Humanos , Teorema de Bayes , Calgranulina B , Células DendríticasRESUMO
Purpose: This study aimed to explore the clinical characteristics of male breast cancer (MBC) patients and the factors influencing their prognosis. Methods: We conducted a retrospective case series analysis of 117 MBC cases who were treated at Zhejiang Cancer Hospital from 2009 to 2022. Cox proportional hazard model was used to identify prognostic factors of MBC. Nomogram was constructed based on these factors, which was further evaluated by C-index and calibration curves. Results: A total of 115 MBC cases were finally included in our analyses, with median diagnosis age of 59 years. Of these cases, 80.0% were estrogen receptor (ER) positive, 79.2% were progesterone receptor (PR) positive, 48.7% were human epidermal growth factor receptor 2 (HER2) negative, and 42.6% had Ki67 levels higher than 15%. 108 (93.9%) cases underwent radical mastectomy, while only 3 (2.6%) received breast-conserving surgery. The Logrank test suggested that lymphocyte-to-monocyte ratio (LMR) was negatively associated with both overall survival (OS) and disease-free survival (DFS) of MBC, while platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) were only positively associated with OS (all P-values < 0.05). Multivariate regression analysis showed that age (HR 1.08, 95% CI 1.03-1.13) was significant prognostic factors for OS. Meanwhile, age (HR 1.06, 95% CI 1.02-1.10), histological differentiation grade (poorly differentiated/undifferentiated vs. well-differentiated: HR 2.55, 95% CI 1.05-6.17), and TNM stage (IV vs. I: HR 31.59, 95% CI 6.01-165.93) were also significant prognostic factors for DFS. Nomograms were developed for DFS, with C-indexes of 0.782, indicating good predictive performance. Conclusion: Increased age, bigger tumor size, higher TNM stage, and lower histological differentiation grade were associated with poor MBC prognosis, and LMR, PLR, and NLR might be potential predictors for MBC prognosis.
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BACKGROUND AND AIMS: The causal relationship between gut microbiota and gout and hyperuricemia (HUA) has not been clarified. The objective of this research was to evaluate the potential causal effects of gut microbiota on HUA and gout using a two-sample Mendelian randomization (MR) approach. METHODS AND RESULTS: Genetic instruments were selected using summary statistics from genome-wide association studies (GWASs) comprising a substantial number of individuals, including 18,473 participants for gut microbiome, 288,649 for serum urate (SU), and 763,813 for gout. Two-sample MR analyses were performed to determine the possible causal associations of gut microbial genera with the risk of HUA and gout using the inverse-variance weighted (IVW) method, and robustness of the results was confirmed by several sensitivity analyses. A reverse MR analysis was conducted on the bacterial taxa that were identified in forward MR analysis. Based on the results of MR analyses, Escherichia-Shigella (OR = 1.05; 95% CI, 1.01-1.08; P = 0.009) exhibited a positive association with SU levels, while Lachnospiraceae NC2004 group (OR = 0.95; 95% CI, 0.92-0.98; P = 0.001) and Family XIII AD3011 group (OR = 0.94; 95% CI, 0.90-0.99; P = 0.015) were associated with a reduced HUA risk. Moreover, Coprococcus 3 (OR = 1.17, 95% CI: 1.01-1.34, P = 0.031) was causally associated with a higher gout risk. In reverse MR analysis, no causal relationships were identified between these bacterial genera and HUA or gout. CONCLUSION: This study provides evidence for a causal association between gut microbial genera and HUA or gout, and further investigations of the underlying mechanism are warranted.
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Microbioma Gastrointestinal , Gota , Hiperuricemia , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/epidemiologia , Hiperuricemia/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Gota/diagnóstico , Gota/genética , ClostridialesRESUMO
OBJECTIVE: To explore the associations between metabolic syndrome (MetS) and its individual components and the risk of rheumatoid arthritis (RA). METHODS: A total of 369,065 individuals were included in the present study based on the UK Biobank. Multivariable Cox proportional hazards regression models were applied to estimate the associations between MetS and its individual components and the risk of RA. Mediation analysis was performed to further assess the potential mediating role of C-reactive protein (CRP) in the relationship between MetS and RA. RESULTS: During a median follow-up period of 12.04 years, a total of 4901 incident RA cases were documented. MetS (hazard ratio [HR] 1.22, 95% CI 1.14-1.30) and 4 of its 5 components (elevated waist circumference [WC; HR 1.21, 95% CI 1.12-1.32], elevated triglyceride [TG] level [HR 1.12, 95% CI 1.05-1.19], reduced high-density lipoprotein cholesterol [HDL-C] level [HR 1.31, 95% CI 1.23-1.39], and hyperglycemia [HR 1.15, 95% CI 1.05-1.25]) were associated with an increased risk of RA. In addition, the risk of RA increased as the number of diagnosed MetS components increased, with the highest risk in participants with all 5 components. Mediation analysis showed that CRP might mediate the association between MetS and RA, accounting for 9.27% of the total effect. CONCLUSION: These findings indicated positive associations between MetS and 4 of its components (WC, TG, HDL-C, and hyperglycemia) and the risk of RA, highlighting the importance of MetS management in the prevention of RA.
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Artrite Reumatoide , Hiperglicemia , Síndrome Metabólica , Humanos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Estudos Prospectivos , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/complicações , Hiperglicemia/complicações , Circunferência da Cintura , Fatores de RiscoRESUMO
BACKGROUND: Observational studies have suggested the potential role of inflammatory factors in the risk of coronary artery disease (CAD). We aimed to perform 2-sample Mendelian randomization (MR) analyses to assess the causal association between circulating cytokines/growth factors and CAD. METHODS AND RESULTS: The instrumental variables for 28 circulating cytokines and growth factors were identified from a genome-wide association study of 8293 European participants. Summary-level data on CAD were derived from a large genome-wide association study (71 602 cases and 260 875 controls). We used the inverse-variance-weighted and Wald ratio methods as our main MR methods. The weighted median, simple median, maximum likelihood, MR pleiotropy residual sum and outlier, and MR-Egger methods were performed as sensitivity analyses. Genetic colocalization analyses were conducted to validate the robustness of our MR findings. We found that genetically predicted circulating levels of macrophage migration inhibitory factor were associated with an increased risk of CAD at the Bonferroni-adjusted level of significance (P<1.79×10-3). The odds ratio was 1.20 (95% CI, 1.08-1.33; P=6.83×10-4) per 1-SD increase in macrophage migration inhibitory factor. Colocalization analyses supported our MR findings. Additionally, we found suggestive evidence between the genetic effects of stem cell growth factor-ß and the risk of CAD (odds ratio, 0.95 [95% CI, 0.91-0.98]; P=0.007). CONCLUSIONS: Our findings suggested a risk-increasing effect of macrophage migration inhibitory factor level on the development of CAD. The roles of these inflammatory factors for CAD warrant further investigation.
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Doença da Artéria Coronariana , Fatores Inibidores da Migração de Macrófagos , Humanos , Doença da Artéria Coronariana/genética , Estudo de Associação Genômica Ampla , Peptídeos e Proteínas de Sinalização Intercelular/genética , CausalidadeRESUMO
A comprehensive overview of the associations between air pollution and the risk of gastrointestinal (GI) diseases has been lacking. We aimed to examine the relationships of long-term exposure to ambient particulate matter (PM) with aerodynamic diameter ≤2.5 µm (PM2.5), 2.5-10 µm (PMcoarse), ≤10 µm (PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx), with the risk of incident GI diseases, and to explore the interplay between air pollution and genetic susceptibility. A total of 465,703 participants free of GI diseases in the UK Biobank were included at baseline. Land use regression models were employed to calculate the residential air pollutants concentrations. Cox proportional hazard models were used to evaluate the associations of air pollutants with the risk of GI diseases. The dose-response relationships of air pollutants with the risk of GI diseases were evaluated by restricted cubic spline curves. We found that long-term exposure to ambient air pollutants was positively associated with the risk of peptic ulcer (PM2.5 : Q4 vs. Q1: hazard ratio (HR) 1.272, 95% confidence interval (CI) 1.179-1.372, NO2: 1.220, 1.131-1.316, and NOx: 1.277, 1.184-1.376) and chronic gastritis (PM2.5: 1.454, 1.309-1.616, PM10 : 1.232, 1.112-1.366, NO2: 1.456, 1.311-1.617, and NOx: 1.419, 1.280-1.574) after Bonferroni correction. Participants with high genetic risk and high air pollution exposure had the highest risk of peptic ulcer, compared to those with low genetic risk and low air pollution exposure (PM2.5: HR 1.558, 95%CI 1.384-1.754, NO2: 1.762, 1.395-2.227, and NOx: 1.575, 1.403-1.769). However, no significant additive or multiplicative interaction between air pollution and genetic risk was found. In conclusion, long-term exposure to ambient air pollutants was associated with increased risk of peptic ulcer and chronic gastritis.
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Poluentes Atmosféricos , Poluição do Ar , Gastrite , Úlcera Péptica , Humanos , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Gastrite/induzido quimicamente , Predisposição Genética para Doença , Dióxido de Nitrogênio/toxicidade , Dióxido de Nitrogênio/análise , Material Particulado/toxicidade , Material Particulado/análise , Úlcera Péptica/induzido quimicamente , Estudos ProspectivosRESUMO
Evidence from epidemiological literature on the association of circulating micronutrients with risk of nonalcoholic fatty liver disease (NAFLD) is inconsistent. We aimed to elucidate the causal relationships using Mendelian randomization (MR). Single-nucleotide polymorphisms associated with 14 circulating micronutrients (ß-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B6, B12, C, D, K1 and zinc) were employed as instrumental variables. Summary level data for NAFLD were obtained from a genome-wide association study (GWAS) meta-analysis of 8434 cases and 770,180 controls (discovery stage) and another two datasets including 1483 NAFLD cases and 17,781 controls (replication stage 1) and 2134 NAFLD cases and 33,433 controls (replication stage 2). Inverse variance-weighted method (IVW) was used as primary analysis, supplemented with a series of sensitivity analysis. Genetically predicted higher ßcarotene levels were suggestively associated with reduced NAFLD risk [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.66-0.99; P = 0.047], whereas the association did not survive the false discovery rates (FDR) correction (PFDR = 0.164). Genetically predicted circulating iron (OR 1.16, 95% CI 1.05-1.29; P = 0.006, PFDR = 0.028), selenium (OR 1.11, 95% CI 1.03-1.20; P = 0.005, PFDR = 0.028) and vitamin B12 (OR 1.08, 95% CI 1.03-1.13; P = 0.002, PFDR = 0.028) were significantly associated with increased risk of NAFLD. Moreover, the findings were consistent in individual datasets (Pheterogeneity > 0.05) and confirmed in sensitivity analysis. Our study provided evidence that circulating iron, selenium and vitamin B12 might be causally linked to the risk of NAFLD, which deserves further exploration of the potential biological mechanism.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Selênio , Humanos , beta Caroteno , Estudo de Associação Genômica Ampla , Ferro , Análise da Randomização Mendeliana , Micronutrientes , Hepatopatia Gordurosa não Alcoólica/genética , Vitamina B 12RESUMO
OBJECTIVE: Milk products are a major part of the western diet, but the role of their effect in rheumatoid arthritis (RA) is controversial. The objective of this study was to explore the relationship between milk products and RA in the United States (US) population. METHODS: In the cross-sectional study, a total of 12,813 participants aged 20years or older were selected from the National Health and Nutrition Examination Survey (NHANES). Consumption of milk products was collected by personal interview, and RA status was obtained by self-reported questionnaires. The association between milk products and RA was estimated by using the weighted logistic regression model. RESULTS: We found a negative association of once a day or more milk products intake with self-reported RA prevalence (odds ratio [OR]: 0.68; 95% confidence interval [CI]: 0.53 to 0.86; P<0.001). A linear trend between consumption of milk products and the prevalence of RA (P<0.01) was also observed. In subgroup analysis, protective effects of milk products on RA were more pronounced in several groups (i.e., Mexican Americans, highly educated and drinking individuals, etc.). However, no interaction effect of stratification variables and the frequency of milk products intake with RA was detected. After imputing missing data, the sensitivity analysis showed the same association. CONCLUSION: This study suggested a negative association between consumption of milk products and RA among US population. Further investigations are warranted to validate the causal association and the underlying mechanism.
Assuntos
Artrite Reumatoide , Leite , Humanos , Estados Unidos/epidemiologia , Animais , Inquéritos Nutricionais , Leite/efeitos adversos , Estudos Transversais , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/complicações , Inquéritos e QuestionáriosRESUMO
Existing reporting checklists lack the necessary level of detail and comprehensiveness to be used in guidelines on Chinese patent medicines (CPM). This study aims to develop a reporting guidance for CPM guidelines based on the Reporting Items of Practice Guidelines in Healthcare (RIGHT) statement. We extracted information from CPM guidelines, existing reporting standards for traditional Chinese medicine (TCM), and the RIGHT statement and its extensions to form the initial pool of reporting items for CPM guidelines. Seventeen experts from diverse disciplines participated in two rounds of Delphi process to refine and clarify the items. Finally, 18 authoritative consultants in the field of TCM and reporting guidelines reviewed and approved the RIGHT for CPM checklist. We added 16 new items and modified two items of the original RIGHT statement to form the RIGHT for CPM checklist, which contains 51 items grouped into seven sections and 23 topics. The new and revised items are distributed across four sections (Basic information, Background, Evidence, and Recommendations) and seven topics: title/subtitle (one new and one revised item), Registration information (one new item), Brief description of the health problem (four new items), Guideline development groups (one revised item), Health care questions (two new items), Recommendations (two new items), and Rationale/explanation for recommendations (six new items). The RIGHT for CPM checklist is committed to providing users with guidance for detailed, comprehensive and transparent reporting, and help practitioners better understand and implement CPM guidelines.
Assuntos
Lista de Checagem , Medicina Tradicional ChinesaRESUMO
Background: Prior epidemiological studies have established a correlation between inflammatory cytokines and inflammatory bowel disease (IBD). However, the nature of this relationship remains uncertain. Mendelian randomization (MR) study has the advantages of avoiding confounding and reverse causality compared with traditional observational research. Objective: We aimed to evaluate whether genetically determined circulating levels of cytokines are associated with the risk of IBD by using the MR approach. Materials and methods: We selected genetic variants associated with circulating levels of 28 cytokines at the genome-wide significance level from a genome-wide association study (GWAS) including 8,293 individuals. Summary-level data for IBD (including Crohn's disease and ulcerative colitis) were obtained from the International Inflammatory Bowel Disease Genetics Consortium and UK Biobank. We performed the primary analysis using the inverse-variance weighted method, as well as sensitivity analyses to test the stability of our results. We subsequently replicated the results of IBD in the UK Biobank dataset. A reverse MR analysis was also conducted to evaluate the possibility of reverse causation. Results: Genetically predicted elevated levels of interleukin-17 (IL-17) and monokine induced by interferon-gamma (MIG) were associated with an increased risk of IBD[odds ratio (OR): 1.52, 95% confidence interval (CI):1.10-2.08, P =0.010 for IL-17 and OR: 1.58, 95% CI: 1.24-2.00, P = 1.60×10-4 for MIG]. Moreover, we observed suggestive associations between ß-NGF and MIP-1ß with the risk of Crohn's disease (OR: 0.71, 95% CI: 0.52-0.98, P = 0.039) and ulcerative colitis (OR: 1.08, 95% CI: 1.01-1.15, P= 0.019). In the reverse MR study, there was no evidence of causal effects of IBD and these cytokines. Conclusion: Our study suggests the potential causal associations of IL-17 and MIG with IBD. Further studies are needed to determine whether IL-17 and MIG or their downstream effectors could be useful in the management of IBD.