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1.
Nutrients ; 15(19)2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37836444

RESUMO

Numerous studies have examined the effects of ketogenic diets (KD) on health-related outcomes through meta-analyses. However, the presence of biases may compromise the reliability of conclusions. Therefore, we conducted an umbrella review to collate and appraise the strength of evidence on the efficacy of KD interventions. We conducted a comprehensive search on PubMed, EMBASE, and the Cochrane Database until April 2023 to identify meta-analyses that investigated the treatment effects of KD for multiple health conditions, which yielded 23 meta-analyses for quantitative analyses. The evidence suggests that KD could increase the levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), the respiratory exchange rate (RER), and could decrease total testosterone and testosterone levels (all p-random effects: <0.05). The combination of KD and physical activity can significantly reduce body weight and increase the levels of LDL-C and cortisol. In addition, KD was associated with seizure reduction in children, which can be explained by the ketosis state as induced by the diet. Furthermore, KD demonstrated a better alleviation effect in refractory childhood epilepsy, in terms of median effective rates for seizure reduction of ≥50%, ≥90%, and seizure freedom. However, the strength of evidence supporting the aforementioned associations was generally weak, thereby challenging their credibility. Consequently, future studies should prioritize stringent research protocols to ascertain whether KD interventions with longer intervention periods hold promise as a viable treatment option for various diseases.


Assuntos
Dieta Cetogênica , Epilepsia Resistente a Medicamentos , Criança , Humanos , LDL-Colesterol , Estudos Transversais , Dieta Cetogênica/métodos , Multimorbidade , Reprodutibilidade dos Testes , Convulsões , Testosterona , Resultado do Tratamento , Metanálise como Assunto
2.
Medicine (Baltimore) ; 102(31): e34469, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37543835

RESUMO

Healthcare-associated infections (HAIs) continue to be the most common adverse event affecting critically ill inpatients in intensive care units (ICUs). Limited data exist in the English literature on the epidemiology of HAIs in ICUs from China. The purpose of this prospective study was to understand the prevalence and trends of HAIs in the ICU to guide clinicians to take effective prevention and control measures. In total, 20 ICU beds in the hospital from January 2012 to December 2019 were selected for surveillance. HAI diagnosis and device-associated infection surveillance were based on the criteria set forth by the original Ministry of Health of the People's Republic of China. The full-time staff for HAI management monitored all patients who stayed in the ICU > 48 hours during the study period and calculated the device utilization ratio and device-associated infection rate. The rate of HAIs and the adjusted rate were 18.78 per 1000 patient-days and 5.17 per 1000 patient-days, respectively. The rates of ventilator-associated pneumonias, catheter-associated urinary tract infections, and central line-associated bloodstream infections were 22.68 per 1000 device-days, 2.40 per 1000 device-days, and 2.27 per 1000 device-days, respectively. A total of 731 pathogenic bacteria were detected in the patients with HAIs. Gram-negative and gram-positive bacteria accounted for 67.44% and 16.83%, respectively. Continuous target monitoring, regular analysis of high-risk factors, and timely intervention measures could effectively reduce HAIs in the ICU. Additionally, these findings could be used for developing new strategies to prevent and control HAIs in ICUs.


Assuntos
Infecções Relacionadas a Cateter , Infecção Hospitalar , Pneumonia Associada à Ventilação Mecânica , Infecções Urinárias , Humanos , Estudos Prospectivos , Infecções Relacionadas a Cateter/prevenção & controle , Atenção Terciária à Saúde , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Unidades de Terapia Intensiva , Hospitais de Ensino , Pneumonia Associada à Ventilação Mecânica/microbiologia , Infecções Urinárias/microbiologia
3.
Intensive Crit Care Nurs ; 79: 103491, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37480701

RESUMO

OBJECTIVES: This study aimed to investigate the prevalence and risk factors for carbapenem-resistant Enterobacterales colonisation/infection at admission and acquisition among patients admitted to the intensive care unit. RESEARCH METHODOLOGY/DESIGN: A prospective and multicentre study. SETTING: This study was conducted in 24 intensive care units in Anhui, China. MAIN OUTCOME MEASURES: Demographic and clinical data were collected, and rectal carbapenem-resistant Enterobacterales colonisation was detected by active screening. Multivariate logistic regression models were used to analyse factors associated with colonisation/infection with carbapenem-resistant Enterobacterales at admission and acquisition during the intensive care unit stay. RESULTS: There were 1133 intensive care unit patients included in this study. In total, 5.9% of patients with carbapenem-resistant Enterobacterales colonisation/infection at admission, and of which 56.7% were colonisations. Besides, 8.5% of patients acquired carbapenem-resistant Enterobacterales colonisation/infection during the intensive care stay, and of which 67.6% were colonisations. At admission, transfer from another hospital, admission to an intensive care unit within one year, colonisation/infection/epidemiological link with carbapenem-resistant Enterobacterales within one year, and exposure to any antibiotics within three months were risk factors for colonisation/infection with carbapenem-resistant Enterobacterales. During the intensive care stay, renal disease, an epidemiological link with carbapenem-resistant Enterobacterales, exposure to carbapenems and beta-lactams/beta-lactamase inhibitors, and intensive care stay of three weeks or longer were associated with acquisition. CONCLUSION: The prevalence of colonisation/infection with carbapenem-resistant Enterobacterales in intensive care units is of great concern and should be monitored systematically. Particularly for the 8.5% prevalence of carbapenem-resistant Enterobacterales acquisition during the intensive care stay needs enhanced infection prevention and control measures in these setting. Surveillance of colonisation/infection with carbapenem-resistant Enterobacterales at admission and during the patient's stay represents an early identification tool to prevent further transmission of carbapenem-resistant Enterobacterales. IMPLICATIONS FOR CLINICAL PRACTICE: Carbapenem-resistant Enterobacterales colonization screening at admission and during the patient's stay is an important tool to control carbapenem-resistant Enterobacterales spread in intensive care units.


Assuntos
Carbapenêmicos , Unidades de Terapia Intensiva , Humanos , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Prevalência , Estudos Prospectivos , Fatores de Risco
4.
Radiol Case Rep ; 16(11): 3186-3190, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34484516

RESUMO

Arteriovenous fistulas (AVFs) caused by an isolated iliac aneurysm rupture and postoperative type II endoleak are rare and life threatening. We report here a case of AVF caused by a ruptured iliac aneurysm and postoperative type II endoleak. The patient was successfully treated by implanting a covered stent to treat the ruptured iliac aneurysm. However, type II endoleak with AVF persisted after the operation and was treated with transiliac vein embolization. The patient recovered uneventfully during the 2-month follow-up period.

5.
Infect Control Hosp Epidemiol ; 42(12): 1506-1510, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33517923

RESUMO

A multicenter study of sharps injuries (SIs) and other blood or body fluid (OBBF) exposures was conducted among 33,156 healthcare workers (HCWs) from 175 hospitals in Anhui, China. In total, 12,178 HCWs (36.7%) had experienced at least 1 SI in the previous 12 months and 8,116 HCWs (24.5%) had experienced at least 1 OBBF exposure during the previous 12 months.


Assuntos
Líquidos Corporais , Ferimentos Penetrantes Produzidos por Agulha , Exposição Ocupacional , Pessoal de Saúde , Humanos , Ferimentos Penetrantes Produzidos por Agulha/epidemiologia , Prevalência
6.
Nano Lett ; 21(1): 634-641, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33264027

RESUMO

Circulating tumor cells (CTCs) have been considered as a potential biomarker for evaluation of cancer metastasis and prognosis, especially in hepatocellular carcinoma (HCC). However, the isolation and detection of rare CTCs in HCC patients face enormous challenges due to omittance and nonspecific binding. We previously designed a small molecular NIR fluoresent agent, named MLP, which had high affinity with a tumor cell-overexpressed enzyme, aminopeptidase N (APN). Based on that, in this work we introduced a novel strategy via coassembling the antiepithelial cell adhesion molecule (EpCAM) antibody and MLPinto theFe3O4 magnetic nanobeads (MB-MLP-EpCAM) to isolate and identify HCC-CTCs coinstantaneously. MB-MLP-EpCAM significantly improved the CTC-capture efficiency (>85%) without sacrificing cell viability (>90%). Most importantly, the advantages of precise dual-targetability, high resolution of fluorescence imaging, and prominent selectivity make our nanoplatform have great potential to achieve in vivo real-time identification and monitoring of CTCs clinically.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Células Neoplásicas Circulantes , Carcinoma Hepatocelular/diagnóstico por imagem , Molécula de Adesão da Célula Epitelial , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Fenômenos Magnéticos , Prognóstico
7.
Semin Dial ; 33(2): 156-162, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32160343

RESUMO

Hemodialysis patients are vulnerable to infectious diseases and frequent receipt of antimicrobial agents. The aim of this study was to describe the prevalence and characteristics of infections and antimicrobials use among hemodialysis outpatients. We utilized the dialysis event surveillance protocol developed by the National Healthcare Safety Network to conduct a prospective multicenter study in Anhui, China. A total of 41 dialysis centers involving 7393 outpatients were included. Fistula was the most common type of vascular access (85.3%), followed by tunneled central line (12.7%), and non-tunneled central line (1.2%). There were 118 dialysis events with an overall pooled events rate of 1.60 per 100 patient-months. Intravenous antimicrobial start, positive blood culture, and pus, redness, or increased swelling at the vascular access site were detected at rates of 0.91, 0.23, and 0.46 per 100 patient-months, respectively. The prevalence of dialysis events was commonly higher in patients with a central line, and lower in patients with a fistula. Hemodialysis outpatients also had the noteworthy risks of nonaccess infections. Older age, female gender, and having a central line were associated with the increased risk of dialysis events. Findings recommend that regular monitoring and improvement strategies are warranted in management of infections among hemodialysis outpatients.


Assuntos
Assistência Ambulatorial , Anti-Infecciosos/uso terapêutico , Infecções Relacionadas a Cateter/epidemiologia , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Adulto , Idoso , Infecções Relacionadas a Cateter/diagnóstico , Infecções Relacionadas a Cateter/microbiologia , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos
8.
J Hosp Infect ; 101(2): 231-239, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30359649

RESUMO

BACKGROUND: The survival of pathogenic organisms in the healthcare environment plays a major role in acquiring healthcare-associated infections (HAIs). AIM: This meta-analysis was conducted to investigate whether pathogenic organisms can be transmitted from roommates and prior room occupants to other inpatients and thus increase the risks of HAIs. METHODS: PubMed (from January 1966) and Embase (from January 1974) were searched to identify studies up to March 2018. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Heterogeneity was assessed using the I-squared statistic. The random-effects model was applied which provides more conservative estimates. Subgroup analyses, cumulative meta-analysis, publication bias diagnosis, and sensitivity analysis were conducted. All the statistical analyses were performed using Stata statistical software version 9.0. RESULTS: Twelve studies including 33,153 subjects reported risk from exposure to infected/colonized roommates and nine studies including 49,839 subjects reported risk from infected/colonized prior room occupants. Exposure to infected/colonized roommates and prior room occupants were associated with the increased risks of HAIs with the same organism (odds ratio (OR) = 2.69, 95% confidence interval (CI) = 1.61-4.49; OR = 1.96, 95% CI = 1.36-2.68; respectively). Sensitivity analyses results did not show major changes in the overall findings. No publication bias was detected. CONCLUSIONS: This meta-analysis showed exposure to infected/colonized roommates and prior room occupants significantly increased the risks of HAIs with the same organism. Health authorities and hospitals should attach higher importance to the fact that current standards or practices for disinfection and isolation are often not sufficient to block transmission of pathogens in the healthcare settings, which may warrant enhanced terminal and intermittent disinfection and strict isolation for reducing HAIs.


Assuntos
Infecção Hospitalar/epidemiologia , Infecção Hospitalar/transmissão , Transmissão de Doença Infecciosa , Exposição Ambiental , Humanos , Controle de Infecções/métodos , Quartos de Pacientes , Medição de Risco
9.
Epidemiol Infect ; 147: e31, 2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30355372

RESUMO

Healthcare-associated infections (HAIs) are a major worldwide public-health problem, but less data are available on the long-term trends of HAIs and antimicrobial use in Eastern China. This study describes the prevalence and long-term trends of HAIs and antimicrobial use in a tertiary care teaching hospital in Hefei, Anhui, China from 2010 to 2017 based on annual point-prevalence surveys. A total of 12 505 inpatients were included; 600 HAIs were recorded in 533 patients, with an overall prevalence of 4.26% and a frequency of 4.80%. No evidence was found for an increasing or decreasing trend in prevalence of HAI over 8 years (trend χ2 = 2.15, P = 0.143). However, significant differences in prevalence of HAI were evident between the surveys (χ2 = 21.14, P < 0.001). The intensive care unit had the highest frequency of HAIs (24.36%) and respiratory tract infections accounted for 62.50% of all cases; Escherichia coli was the most common pathogen (16.67%). A 44.13% prevalence of antimicrobial use with a gradually decreasing trend over time was recorded. More attention should be paid to potential high-risk clinical departments and HAI types with further enhancement of rational antimicrobial use.

10.
Oncol Lett ; 16(4): 4291-4296, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30214563

RESUMO

The aim of the study was to investigate the expression of tumor suppressor gene p53 and MMP-9 in non-small cell lung cancer (NSCLC) before and after chemotherapy, and investigate its association with the effect of chemotherapy and prognosis. Fifty-eight elderly NSCLC patients comprised the observation group. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of p53 and MMP-9 in lung cancer tissues before and after chemotherapy. Immunohistochemistry and western blot analysis were used to detect the expression of p53 and MMP-9 proteins in NSCLC tissue before and after chemotherapy. Terminal deoxynucleotidyl transferase nick end-labeling (TUNEL) was used to detect apoptotic cells. The association between the effect of chemotherapy and the expression of p53 and MMP-9 in lung cancer tissues was analysed. RT-qPCR results showed that the expression of p53 and MMP-2 mRNA in the tumor tissue after chemotherapy was significantly lower than that in the tumor tissue before chemotherapy. Western blot analysis revealed that the expression of p53 and MMP-2 protein in the tumor tissue after chemotherapy was significantly decreased. The positive expression of p53 and MMP-2 in lung cancer tissues before chemotherapy was 76.25 and 71.25%, respectively, and were reduced to 27.50 and 23.75%, respectively, after chemotherapy. After chemotherapy, the positive rates of p53 and MMP-2 were significantly lower than those before chemotherapy. TUNEL results showed that the apoptosis index increased significantly after chemotherapy. Efficiency of chemotherapy in patients with a negative expression of p53 and MMP-2 in lung cancer before chemotherapy was significantly higher than that in patients with a positive p53 and MMP-2 expression. A significant difference was found in the expression levels of p53 and MMP-2 in lung cancer before and after chemotherapy. The findings of the present study indicate that the expression levels of p53 and MMP-2 can be used as a predictor of chemotherapy sensitivity.

11.
Mol Med Rep ; 6(1): 105-10, 2012 07.
Artigo em Inglês | MEDLINE | ID: mdl-22505023

RESUMO

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder that predominantly affects women of childbearing age, with a female-to-male ratio of approximately 9:1. Previous findings indicated that male cases of SLE were associated with Klinefelter's syndrome (47, XXY), whereas females with Turner's syndrome (45, X0) did not contract SLE. Additionally, duplicated Toll-like receptor 7 (TLR7) was found to promote lupus-like disease. Consequently, the aim of this study was to evaluate whether the TLR7 gene served as a genetic marker for the development of SLE. A case-control study was performed on one tag single nucleotide polymorphism TLR7 rs1634323 in a population with 507 SLE patients and 513 healthy controls. Genotyping was determined by the TaqMan genotyping assay using the ABI 7300 real-time reverse transcription polymerase chain reaction system. The results showed a significantly elevated risk of SLE with the rs1634323 AG genotype in females (P = 0.040, OR = 1.897, 95% CI 1.031-3.491), whereas a similar association was not replicated in males (P = 0.303, OR = 0.338, 95% CI 0.043-2.656). In a subgroup analysis by clinical manifestation of lupus nephritis, no significant differences were found. These findings indicate that the TLR7 gene rs1634323 polymorphism may contribute to SLE susceptibility in females.


Assuntos
Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Receptor 7 Toll-Like/genética , Adolescente , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Adulto Jovem
13.
Clin Exp Med ; 11(4): 245-50, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21487830

RESUMO

Recently, Th17 cell-associated responses have received growing attention; however, the role of IL-22 (a cytokines also produced by Th17 cells) in the pathogenesis of systemic lupus erythematosus (SLE) has not been widely explored. In this study, we analyze the frequencies of IL-22-positive CD4+/CD8+ T cells in peripheral blood mononuclear cells (PBMCs) from patients with SLE and their correlations with disease activity and clinical data. Five-color flow cytometry (FCM) was used to assess IL-22 production of CD4+/CD8+ T cells in PBMCs from 31 patients with SLE and 22 healthy control subjects, following stimulation ex vivo with phorbol 12-myristate 13-acetate and ionomycin for 4 h. Results showed that the percentages of IL-22-positive CD4+ T cells were increased in the PBMCs of patients with SLE compared with healthy control subjects, whereas there were no significant differences in the percentages of IL-22-positive CD8+ T cells. There was a strong positive correlation between the proportion of CD4+ T cells expressing IL-22 and SLEDAI score (r (s) = 0.65, P < 0.001). Furthermore, the frequencies of IL-22-positive CD4+ T cells were significantly higher in patients with SLE with nephritis than those without nephritis (Z = -2.72, P < 0.01). In conclusion, increased frequencies of IL-22-positive CD4+ T cells in patients with SLE and positive correlation with SLEDAI score and lupus nephritis suggest that this cytokine may be implicated in the pathogenesis of the disease.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Interleucinas/biossíntese , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Adulto , Feminino , Citometria de Fluxo , Humanos , Leucócitos Mononucleares/química , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/patologia , Masculino , Pessoa de Meia-Idade , Interleucina 22
14.
Mutagenesis ; 26(4): 507-11, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21367814

RESUMO

Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune diseases, which affects multiple organ systems such as kidney. The imbalance of T-helper 1 (Th1)/Th2 cells is critical in the pathogenesis of SLE. The T-cell immunoglobulin mucin (TIM) proteins comprise a family of cell surface molecules expressed on T cells that regulate Th1- and Th2-cell-mediated immunity. Recent work has found increased expression of TIM-1 and TIM-3 ligand (galactin-9) mRNA in SLE patients and implied that TIM proteins might be involved in the pathogenesis of SLE. In this study, genotyping of single-nucleotide polymorphisms (SNPs) was performed for TIM-1 (rs1501909 and rs12522248) and TIM-3 (rs9313439 and rs10515746) in 202 SLE patients and 217 healthy individuals in a Chinese population. Results showed no significant differences existed between the patients with SLE and the controls as well as SLE patients with nephritis and those without nephritis, in all four SNPs. The findings suggest that the polymorphisms of TIM gene family might not contribute to SLE susceptibility in the Chinese population. However, it should be noted that the statistical power of our study is relatively low, which likely did not have adequate power to detect the actual correlation between the selected SNPs and SLE susceptibility; moreover, we cannot discard a possible association of other variants within the region covering TIM with SLE as a genetic risk factor, with larger samples in different populations.


Assuntos
Povo Asiático/genética , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Glicoproteínas de Membrana/genética , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores Virais/genética , Adulto , Estudos de Casos e Controles , China/etnologia , Feminino , Frequência do Gene/genética , Haplótipos/genética , Receptor Celular 1 do Vírus da Hepatite A , Receptor Celular 2 do Vírus da Hepatite A , Humanos , Masculino
15.
Acta Pharmacol Sin ; 31(4): 443-9, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20228825

RESUMO

AIM: To investigate the efficacy of glycyrrhizin (GL) combined with salbutamol (SA) as an anti-asthma therapy. METHODS: Rat lung beta2-adrenergic receptor (beta(2)-AR) mRNA level was measured by real-time RT PCR. Intracellular cAMP accumulation was evaluated with a reporter gene assay. An in vitro acetylcholine-induced guinea pig tracheal strip contraction model was used to test the relaxing effects of GL and SA. The anti-inflammatory effects of GL and SA were tested using tumor necrosis factor-alpha-induced NF-kappaB transcriptional activation reporter assay, I-kappaB Western blotting and interleukin-8 ELISA. An in vivo guinea pig asthma model was used to prove further the synergistic effect of GL and SA. RESULTS: GL (0.3 micromol/L) increased mRNA levels of beta(2)-AR in vivo and the accumulation of cAMP in vitro. The combination of GL and SA also resulted in significant complementary anti-inflammatory effects via inhibition of NF-kappaB activation, degradation of I-kappaB and production of interleukin-8. A significant synergistic effect of the combination was detected both in vitro and in vivo in a guinea pig mode. CONCLUSION: The results demonstrate that GL and SA have synergistic anti-asthmatic effects and offer the possibility of a therapeutic application of GL in combination with beta(2)-AR agonists in the treatment of asthma.


Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Albuterol/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Ácido Glicirrízico/uso terapêutico , Receptores Adrenérgicos beta 2/metabolismo , Agonistas de Receptores Adrenérgicos beta 2 , Agonistas Adrenérgicos beta/farmacologia , Albuterol/farmacologia , Animais , Antiasmáticos/farmacologia , Linhagem Celular , AMP Cíclico/metabolismo , Sinergismo Farmacológico , Ácido Glicirrízico/farmacologia , Cobaias , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , NF-kappa B/imunologia , RNA Mensageiro/genética , Ratos , Receptores Adrenérgicos beta 2/genética , Traqueia/efeitos dos fármacos , Fator de Necrose Tumoral alfa/imunologia
16.
PLoS Genet ; 6(2): e1000841, 2010 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-20169177

RESUMO

Systemic lupus erythematosus is a complex and potentially fatal autoimmune disease, characterized by autoantibody production and multi-organ damage. By a genome-wide association study (320 patients and 1,500 controls) and subsequent replication altogether involving a total of 3,300 Asian SLE patients from Hong Kong, Mainland China, and Thailand, as well as 4,200 ethnically and geographically matched controls, genetic variants in ETS1 and WDFY4 were found to be associated with SLE (ETS1: rs1128334, P = 2.33x10(-11), OR = 1.29; WDFY4: rs7097397, P = 8.15x10(-12), OR = 1.30). ETS1 encodes for a transcription factor known to be involved in a wide range of immune functions, including Th17 cell development and terminal differentiation of B lymphocytes. SNP rs1128334 is located in the 3'-UTR of ETS1, and allelic expression analysis from peripheral blood mononuclear cells showed significantly lower expression level from the risk allele. WDFY4 is a conserved protein with unknown function, but is predominantly expressed in primary and secondary immune tissues, and rs7097397 in WDFY4 changes an arginine residue to glutamine (R1816Q) in this protein. Our study also confirmed association of the HLA locus, STAT4, TNFSF4, BLK, BANK1, IRF5, and TNFAIP3 with SLE in Asians. These new genetic findings may help us to gain a better understanding of the disease and the functions of the genes involved.


Assuntos
Povo Asiático/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Peptídeos e Proteínas de Sinalização Intracelular/genética , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único/genética , Proteína Proto-Oncogênica c-ets-1/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Alelos , Estudos de Coortes , Proteínas de Ligação a DNA , Feminino , Haplótipos/genética , Humanos , Fatores Reguladores de Interferon/genética , Leucócitos Mononucleares/metabolismo , Desequilíbrio de Ligação/genética , Lúpus Eritematoso Sistêmico/enzimologia , Masculino , Proteínas de Membrana/genética , Proteínas Nucleares/genética , Análise de Componente Principal , Reprodutibilidade dos Testes , Fator de Transcrição STAT4/genética , Proteína 3 Induzida por Fator de Necrose Tumoral alfa , Quinases da Família src/genética
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