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1.
Adv Exp Med Biol ; 1255: 83-98, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32949392

RESUMO

Chronic obstructive pulmonary disease (COPD) is a lung disease affected by both genetic and environmental factors. Therefore, the role of epigenetics in the pathogenesis of COPD has attracted much attention. As one of the three epigenetic mechanisms, DNA methylation has been extensively studied in COPD. The present review aims at overviewing the effect of DNA methylation on etiology, pathogenesis, pathophysiological changes, and complications of COPD. The clarification of aberrant methylation of target genes, which play important roles in the initiation and progression of COPD, will provide new disease-specific biomarker and targets for early diagnosis and therapy.


Assuntos
Metilação de DNA , Doença Pulmonar Obstrutiva Crônica/genética , Epigênese Genética , Epigenômica , Humanos
2.
Sci Adv ; 6(33): eabb7238, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32851183

RESUMO

Cigarette smoking, the leading cause of chronic obstructive pulmonary disease (COPD), has been implicated as a risk factor for severe disease in patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we show that mice with lung epithelial cell-specific loss of function of Miz1, which we identified as a negative regulator of nuclear factor κB (NF-κB) signaling, spontaneously develop progressive age-related changes resembling COPD. Furthermore, loss of Miz1 up-regulates the expression of Ace2, the receptor for SARS-CoV-2. Concomitant partial loss of NF-κB/RelA prevented the development of COPD-like phenotype in Miz1-deficient mice. Miz1 protein levels are reduced in the lungs from patients with COPD, and in the lungs of mice exposed to chronic cigarette smoke. Our data suggest that Miz1 down-regulation-induced sustained activation of NF-κB-dependent inflammation in the lung epithelium is sufficient to induce progressive lung and airway destruction that recapitulates features of COPD, with implications for COVID-19.


Assuntos
Células Epiteliais/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Pulmão/metabolismo , Peptidil Dipeptidase A/metabolismo , Fenótipo , Proteínas Inibidoras de STAT Ativados/genética , Doença Pulmonar Obstrutiva Crônica/genética , Ubiquitina-Proteína Ligases/genética , Regulação para Cima/genética , Animais , Betacoronavirus , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Técnicas de Inativação de Genes , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pandemias , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Proteínas Inibidoras de STAT Ativados/metabolismo , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Transdução de Sinais/genética , Fumar/efeitos adversos , Fator de Transcrição RelA/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
3.
Medicine (Baltimore) ; 99(31): e21479, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756173

RESUMO

BACKGROUND: To comprehensively evaluate the association between the polymorphism of matrix metalloproteinase-9 (MMP-9)-C1562T (rs3918242) and susceptibility to chronic obstructive pulmonary disease (COPD) in middle-aged and elderly patients through Meta-analysis. METHODS: PubMed, EMBASE, CNKI, Wanfang, VIP, and other databases were searched by computer in the inception to August 2019 to collect all the case-control studies that met the inclusion criteria in this literature. Meta-analysis was performed using Stata 15.0, including the OR value calculations of the association between the merged MMP-9-C1562T polymorphism and the COPD susceptibility. Subgroup analysis, sensitivity analysis, and publication bias test were also performed. A total of 13 literature were included in this Meta-analysis with a total of 2512 cases and 2716 controls. RESULTS: The results have shown that the OR of MMP-9-C1562T T allele to C allele was 0.35 (95% confidence interval [CI]: 0.23-0.52, P < .01). The subgroup analysis of ethnicity result showed that the merged OR of MMP-9-C1562T T allele to C allele was 0.24 (95% CI: 0.17-0.34, P < .01) in Caucasian while the merged OR was 0.62 (95% CI: 0.22-1.70, P > .05) in Asian. However, there were no statistically significant models in the dominant, recessive, homozygote and heterozygote genetic models. CONCLUSION: The MMP-9-C1562T polymorphism was associated with the susceptibility to middle-aged and elderly COPD patients. Compared with T allele, C allele increased the risk of disease, especially in Caucasian, but not found in Asian.


Assuntos
Predisposição Genética para Doença/genética , Metaloproteinase 9 da Matriz/genética , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Idoso , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
4.
Medicine (Baltimore) ; 99(31): e21543, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756209

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a multifactorial disease with gene-environment interaction leading to airflow limitation through the respiratory tract. Reports on the association of matrix metalloproteinase 12 (MMP-12) polymorphisms with COPD have been controversial. A new systematic evaluation which could examine whether MMP-12 mutations are associated with the susceptibility to COPD is needed. METHODS: We will search PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure and Google Scholar to obtain eligible case-control studies for meta-analysis. The time is limited from the construction of the library to July 2020. Two investigators systematically will extract relevant data within those included studies.The odds ratio and 95% confidence intervals will be used to assess the genetic association between the allelic, dominant and recessive models of MMP-12 gene polymorphisms and COPD risk. Stata 12.0 software and Revman 5.3 will be adopted for statistical analysis. This protocol reported under the Preferred Reporting ltems for Systematic Reviews and Meta-Analyses Protocols statement. RESULTS: This study will provide a better understanding of the association between MMP-12 polymorphisms and COPD risk. CONCLUSION: Publishing this protocol will minimise the possibility of bias due to post hoc changes to the analysis protocol.


Assuntos
Metaloproteinase 12 da Matriz/genética , Doença Pulmonar Obstrutiva Crônica/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Projetos de Pesquisa
5.
Eur J Clin Invest ; 50(10): e13382, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32780415

RESUMO

In barely nine months, the pandemic known as COVID-19 has spread over 200 countries, affecting more than 22 million people and causing over than 786 000 deaths. Elderly people and patients with previous comorbidities such as hypertension and diabetes are at an increased risk to suffer a poor prognosis after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although the same could be expected from patients with chronic obstructive pulmonary disease (COPD), current epidemiological data are conflicting. This could lead to a reduction of precautionary measures in these patients, in the context of a particularly complex global health crisis. Most COPD patients have a long history of smoking or exposure to other harmful particles or gases, capable of impairing pulmonary defences even years after the absence of exposure. Moreover, COPD is characterized by an ongoing immune dysfunction, which affects both pulmonary and systemic cellular and molecular inflammatory mediators. Consequently, increased susceptibility to viral respiratory infections have been reported in COPD, often worsened by bacterial co-infections and leading to serious clinical outcomes. The present paper is an up-to-date review that discusses the available research regarding the implications of coronavirus infection in COPD. Although validation in large studies is still needed, COPD likely increases SARS-CoV-2 susceptibility and increases COVID-19 severity. Hence, specific mechanisms to monitor and assess COPD patients should be addressed in the current pandemic.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Betacoronavirus , Biomassa , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Suscetibilidade a Doenças , Exposição Ambiental/estatística & dados numéricos , Predisposição Genética para Doença , Humanos , Pandemias , Material Particulado , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/imunologia , Índice de Gravidade de Doença , Fumaça , Fumar/epidemiologia , Fumar/imunologia
6.
Lancet Respir Med ; 8(7): 696-708, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32649918

RESUMO

BACKGROUND: Genetic factors influence chronic obstructive pulmonary disease (COPD) risk, but the individual variants that have been identified have small effects. We hypothesised that a polygenic risk score using additional variants would predict COPD and associated phenotypes. METHODS: We constructed a polygenic risk score using a genome-wide association study of lung function (FEV1 and FEV1/forced vital capacity [FVC]) from the UK Biobank and SpiroMeta. We tested this polygenic risk score in nine cohorts of multiple ethnicities for an association with moderate-to-severe COPD (defined as FEV1/FVC <0·7 and FEV1 <80% of predicted). Associations were tested using logistic regression models, adjusting for age, sex, height, smoking pack-years, and principal components of genetic ancestry. We assessed predictive performance of models by area under the curve. In a subset of studies, we also studied quantitative and qualitative CT imaging phenotypes that reflect parenchymal and airway pathology, and patterns of reduced lung growth. FINDINGS: The polygenic risk score was associated with COPD in European (odds ratio [OR] per SD 1·81 [95% CI 1·74-1·88] and non-European (1·42 [1·34-1·51]) populations. Compared with the first decile, the tenth decile of the polygenic risk score was associated with COPD, with an OR of 7·99 (6·56-9·72) in European ancestry and 4·83 (3·45-6·77) in non-European ancestry cohorts. The polygenic risk score was superior to previously described genetic risk scores and, when combined with clinical risk factors (ie, age, sex, and smoking pack-years), showed improved prediction for COPD compared with a model comprising clinical risk factors alone (AUC 0·80 [0·79-0·81] vs 0·76 [0·75-0·76]). The polygenic risk score was associated with CT imaging phenotypes, including wall area percent, quantitative and qualitative measures of emphysema, local histogram emphysema patterns, and destructive emphysema subtypes. The polygenic risk score was associated with a reduced lung growth pattern. INTERPRETATION: A risk score comprised of genetic variants can identify a small subset of individuals at markedly increased risk for moderate-to-severe COPD, emphysema subtypes associated with cigarette smoking, and patterns of reduced lung growth. FUNDING: US National Institutes of Health, Wellcome Trust.


Assuntos
Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/genética , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Volume Expiratório Forçado , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Fatores de Risco , Capacidade Vital
9.
J Infect Dis ; 222(4): 556-563, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32526012

RESUMO

Patients who died from COVID-19 often had comorbidities, such as hypertension, diabetes, and chronic obstructive lung disease. Although angiotensin-converting enzyme 2 (ACE2) is crucial for SARS-CoV-2 to bind and enter host cells, no study has systematically assessed the ACE2 expression in the lungs of patients with these diseases. Here, we analyzed over 700 lung transcriptome samples from patients with comorbidities associated with severe COVID-19 and found that ACE2 was highly expressed in these patients compared to control individuals. This finding suggests that patients with such comorbidities may have higher chances of developing severe COVID-19. Correlation and network analyses revealed many potential regulators of ACE2 in the human lung, including genes related to histone modifications, such as HAT1, HDAC2, and KDM5B. Our systems biology approach offers a possible explanation for increased COVID-19 severity in patients with certain comorbidities.


Assuntos
Infecções por Coronavirus/epidemiologia , Pulmão/enzimologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/epidemiologia , Estudos de Casos e Controles , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/genética , Comorbidade , Doença das Coronárias/epidemiologia , Doença das Coronárias/genética , Infecções por Coronavirus/enzimologia , Infecções por Coronavirus/genética , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/genética , Epigenômica , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/genética , Masculino , Pandemias , Peptidil Dipeptidase A/genética , Pneumonia Viral/enzimologia , Pneumonia Viral/genética , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/genética , Índice de Gravidade de Doença , Biologia de Sistemas , Transcriptoma
10.
Life Sci ; 256: 117829, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32454159

RESUMO

BACKGROUND: The development of Chronic Obstructive Pulmonary Disease (COPD) has been assessed and divided into slow development (SD), normal development (ND) and quick development (QD). Little is known about the plasma proteome characters among these three phenotypes. METHODS: We performed a comparative proteomic analysis in the plasma of normal control (NC), SD, ND and QD phenotype COPD patients using isobaric tags for relative and absolute quantitation (iTRAQ) technique. RESULTS: A total of 683 proteins were successfully identified in the plasma samples, of which 394 were considered as high-quality proteins (95% confidential peptides ≥ 2). Further, a total of 25, 19 and 27 different abundant proteins (DAPs) were identified in SD, ND and QD groups, respectively. Gene ontology (GO) classification analysis of all DAPs showed that immune system process (GO:0002376) were the most significant. The pathway enrichment analysis showed that innate immune response (GO:0045087), receptor-mediated endocytosis (GO:0006898) and proteolysis (GO:0006508) were the branch-end terms. Notably, the 15 QD special DAPs were considered as potential markers for identify patient might have quick development COPD, and thus provided more aggressive treatment strategy for these patients. CONCLUSION: This work provides an insight into global plasma proteome profiles among the SD, ND and QD phenotypes of COPD patients. The most significant GO terms that the DAPs enriched in were immune system related terms. In addition, the 15 QD specific DPAs provided candidates of potential markers to predict the development types of COPD patients.


Assuntos
Imunidade Inata/imunologia , Proteínas/metabolismo , Proteômica/métodos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Idoso , Feminino , Ontologia Genética , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Proteoma/metabolismo , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/imunologia
11.
Obesity (Silver Spring) ; 28(9): 1586-1589, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32428380

RESUMO

OBJECTIVE: Mortality from coronavirus disease 2019 (COVID-19) is increased in patients with chronic obstructive pulmonary disease (COPD). Furthermore, higher BMI is related to severe disease. Severe acute respiratory syndrome coronavirus 2 utilizes angiotensin converting enzyme 2 (ACE2) to gain cellular entry. METHODS: Whether ACE2 bronchial epithelial expression is increased in COPD patients who have overweight compared with those who do not was investigated by RNA sequencing. RESULTS: Increased ACE2 expression was observed in patients with COPD with overweight (mean BMI, 29 kg/m2 ) compared with those without overweight (mean BMI, 21 kg/m2 ) (P = 0.004). CONCLUSIONS: Increased ACE2 expression may cause increased severe acute respiratory syndrome coronavirus 2 infection of the respiratory tract. Overweight COPD patients may be at greater risk for developing severe COVID-19.


Assuntos
Brônquios , Epitélio/metabolismo , Sobrepeso/complicações , Peptidil Dipeptidase A/genética , Doença Pulmonar Obstrutiva Crônica/genética , Idoso , Betacoronavirus , Infecções por Coronavirus , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral , Doença Pulmonar Obstrutiva Crônica/complicações
13.
Am J Physiol Lung Cell Mol Physiol ; 319(1): L48-L60, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32460521

RESUMO

Chronic obstructive pulmonary disease (COPD) is associated with features of accelerated aging, including cellular senescence, DNA damage, oxidative stress, and extracellular matrix (ECM) changes. We propose that these features are particularly apparent in patients with severe, early-onset (SEO)-COPD. Whether fibroblasts from COPD patients display features of accelerated aging and whether this is also present in relatively young SEO-COPD patients is unknown. Therefore, we aimed to determine markers of aging in (SEO)-COPD-derived lung fibroblasts and investigate the impact on ECM. Aging hallmarks and ECM markers were analyzed in lung fibroblasts from SEO-COPD and older COPD patients and compared with fibroblasts from matched non-COPD groups (n = 9-11 per group), both at normal culture conditions and upon Paraquat-induced senescence. COPD-related differences in senescence and ECM expression were validated in lung tissue. Higher levels of cellular senescence, including senescence-associated ß-galactosidase (SA-ß-gal)-positive cells (19% for COPD vs. 13% for control) and p16 expression, DNA damage (γ-H2A.X-positive nuclei), and oxidative stress (MGST1) were detected in COPD compared with control-derived fibroblasts. Most effects were also different in SEO-COPD, with SA-ß-gal-positive cells only being significant in SEO-COPD vs. matched controls. Lower decorin expression in COPD-derived fibroblasts correlated with higher p16 expression, and this association was confirmed in lung tissue. Paraquat treatment induced cellular senescence along with clear changes in ECM expression, including decorin. Fibroblasts from COPD patients, including SEO-COPD, display higher levels of cellular senescence, DNA damage, and oxidative stress. The association between cellular senescence and ECM expression changes may suggest a link between accelerated aging and ECM dysregulation in COPD.


Assuntos
Senescência Celular , Matriz Extracelular/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Adulto , Idade de Início , Biomarcadores/metabolismo , Células Cultivadas , Dano ao DNA , Feminino , Fibroblastos/patologia , Regulação da Expressão Gênica , Humanos , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Pessoa de Meia-Idade , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Estresse Oxidativo , Paraquat/toxicidade , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/fisiopatologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-32233789

RESUMO

Air-liquid interface (ALI) cultures are ex vivo models that are used extensively to study the epithelium of patients with chronic respiratory diseases. However, the in vitro conditions impose a milieu different from that encountered in the patient in vivo, and the degree to which this alters gene expression remains unclear. In this study we employed RNA sequencing to compare the transcriptome of fresh brushings of nasal epithelial cells with that of ALI-cultured epithelial cells from the same patients. We observed a strong correlation between cells cultured at the ALI and cells obtained from the brushed nasal epithelia: 96% of expressed genes showed similar expression profiles, although there was greater similarity between the brushed samples. We observed that while the ALI model provides an excellent representation of the in vivo airway epithelial transcriptome for mechanistic studies, several pathways are affected by the change in milieu.


Assuntos
Mucosa Nasal/metabolismo , Doença Pulmonar Obstrutiva Crônica/genética , Mucosa Respiratória/metabolismo , Transcriptoma , Idoso , Ar , Fumar Cigarros/efeitos adversos , Meios de Cultura/química , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Anotação de Sequência Molecular , Mucosa Nasal/patologia , Cultura Primária de Células , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Mucosa Respiratória/patologia , Análise de Sequência de RNA , Conchas Nasais/metabolismo , Conchas Nasais/patologia
17.
Clin Sci (Lond) ; 134(7): 751-763, 2020 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-32227160

RESUMO

The numbers of macrophages are increased in the lungs of chronic obstructive pulmonary disease (COPD) patients. COPD lung macrophages have reduced ability to phagocytose microbes and efferocytose apoptotic cells. Inhaled corticosteroids (ICSs) are widely used anti-inflammatory drugs in COPD; however, their role beyond suppression of cytokine release has not been explored in COPD macrophages. We have examined the effects of corticosteroids on COPD lung macrophage phenotype and function. Lung macrophages from controls and COPD patients were treated with corticosteroids; effects on gene and protein expression of CD163, CD164, CD206, MERTK, CD64, CD80 and CD86 were studied. We also examined the effect of corticosteroids on the function of CD163, MERTK and cluster of differentiation 64 (CD64). Corticosteroid increased CD163, CD164, CD206 and MERTK expression and reduced CD64, CD80 and CD86 expression. We also observed an increase in the uptake of the haemoglobin-haptoglobin complex (CD163) from 59 up to 81% and an increase in efferocytosis of apoptotic neutrophils (MERTK) from 15 up to 28% following corticosteroid treatment. We observed no effect on bacterial phagocytosis. Corticosteroids alter the phenotype and function of COPD lung macrophages. Our findings suggest mechanisms by which corticosteroids exert therapeutic benefit in COPD, reducing iron available for bacterial growth and enhancing efferocytosis.


Assuntos
Corticosteroides/farmacologia , Dexametasona/farmacologia , Pulmão/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Idoso , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Apoptose/efeitos dos fármacos , Estudos de Casos e Controles , Células Cultivadas , Técnicas de Cocultura , Feminino , Regulação da Expressão Gênica , Humanos , Ferro/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Neutrófilos/patologia , Fenótipo , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Receptores de IgG/genética , Receptores de IgG/metabolismo , Transdução de Sinais , c-Mer Tirosina Quinase/genética , c-Mer Tirosina Quinase/metabolismo
19.
Gene ; 744: 144633, 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32240778

RESUMO

BACKGROUND: Several studies have examined the association between transforming growth factor-ß (TGF-ß) genetic polymorphisms and chronic obstructive pulmonary disease (COPD) risk, but the results remained inconclusive and controversial. AIMS: We aimed to examine the correlation between TGF-ß genetic polymorphisms and COPD risk through a comprehensive meta-analysis. Additionally, changes in circulating TGF-ß concentrations across genotypes of TGF-ß genetic polymorphisms were analyzed. METHODS: Literature search, quality assessment, and data extraction were completed independently and in duplicate. Data are expressed in odds ratio (OR) or weighted mean difference (WMD) with 95% confidence interval (CI). RESULTS: A total of 12 articles, involving 14 independent studies and 7 170 participants, were meta-analyzed for the correlation of five polymorphisms (rs2241712, rs1800469, rs1982073, rs6957, and rs2241718) in TGF-ß gene with COPD risk. Under the allele model, no statistical significance was observed for all polymorphisms associated with COPD risk. Subsidiary analyses indicated that country, COPD stage, and diagnosis of COPD were potential sources of between-study heterogeneity. Filled full plots revealed no missing studies for all studied polymorphisms, except rs1982073. Genotype-phenotype analyses showed that carriers of rs1800469 CT genotype had significantly higher concentrations of circulating TGF-ß than those with CC genotype in COPD patients (WMD: 0.28 pg/ml, 95% CI: 0.01 to 0.56). CONCLUSION: Our findings failed to support the candidacy of TGF-ß gene in the development of COPD, whereas the contribution of TGF-ß gene to COPD might be ethnicity- and stage-dependent.


Assuntos
Doença Pulmonar Obstrutiva Crônica/genética , Fator de Crescimento Transformador beta1/genética , Correlação de Dados , Genótipo , Humanos , Polimorfismo Genético , Doença Pulmonar Obstrutiva Crônica/sangue , Fatores de Risco , Fator de Crescimento Transformador beta1/sangue
20.
Asian Pac J Cancer Prev ; 21(3): 667-673, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32212792

RESUMO

BACKGROUND: Lung cancer coexisting with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) can lead to poor prognosis.  Telomere-related polymorphisms may be implicated in the pathogenesis of these three lung diseases.  As to elucidate the mechanism of lung cancer via IPF or COPD may enable early detection and early treatment of the disease, we firstly examined the association between telomere-related polymorphisms and the risk of IPF and COPD in a case-control study. MATERIALS AND METHODS: A total of 572 patients with IPF (n = 155) or COPD (n = 417), who were derived from our on-going cohort study, and controls (n = 379), who were derived from our previous case-control study, were included in this study.  Telomerase reverse transcriptase (TERT) rs2736100, telomere RNA component (TERC) rs1881984, and oligonucleotide/oligosaccharide-binding fold containing1 (OBFC1) rs11191865 were genotyped with real-time PCR using TaqMan fluorescent probes. Unconditional logistic regression was used to assess the adjusted odds ratios and 95% confidence intervals. RESULTS: TERT rs2736100 was significantly associated with the risk of IPF; increases in the number of this risk allele increased the risk of IPF (Ptrend = 0.008).  Similarly, TERT rs2736100 was associated with the risk of COPD.  In regard to the combined action of the three loci, increasing numbers of "at-risk" genotypes increased the risk of IPF in a dose-dependent manner (P trend=0.003). CONCLUSIONS: TERT rs2736100 was associated with the risks of both IPF and COPD in a Japanese population. A combination of the "at-risk" genotypes might be important to identify the population at risk for IPF more clearly.


Assuntos
Fibrose Pulmonar Idiopática/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Telomerase/genética , Feminino , Humanos , Masculino , Sistema de Registros , Fatores de Risco , Tabaco/efeitos adversos
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