RESUMO
PURPOSE: Patients with type 2 diabetes (T2D) have demonstrated a higher risk for developing more severe cases of COVID-19, but the complex genetic mechanism between them is still unknown. The aim of the present study was to untangle this relationship using genetically based approaches. METHODS: By leveraging large-scale genome-wide association study (GWAS) summary statistics of T2D and COVID-19 severity, linkage disequilibrium score regression and Mendelian randomization (MR) analyses were utilized to quantify the genetic correlations and causal relationships between the two traits. Gene-based association and enrichment analysis were further applied to identify putative functional pathways shared between T2D and COVID-19 severity. RESULTS: Significant, moderate genetic correlations were detected between T2D and COVID-19 hospitalization (rg = 0.156, SE = 0.057, p = 0.005) or severe disease (rg = 0.155, SE = 0.057, p = 0.006). MR analysis did not support evidence for a causal effect of T2D on COVID-19 hospitalization (OR 1.030, 95% CI 0.979, 1.084, p = 0.259) or severe disease (OR 0.999, 95% CI 0.934, 1.069, p = 0.982). Genes having pgene < 0.05 for both T2D and COVID-19 severe were significantly enriched for biological pathways, such as response to type I interferon, glutathione derivative metabolic process and glutathione derivative biosynthetic process. CONCLUSIONS: Our findings further confirm the comorbidity of T2D and COVID-19 severity, but a non-causal impact of T2D on severe COVID-19. Shared genetically modulated molecular mechanisms underlying the co-occurrence of the two disorders are crucial for identifying therapeutic targets.
Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Estudo de Associação Genômica Ampla , COVID-19/epidemiologia , COVID-19/genética , COVID-19/complicações , Comorbidade , Glutationa/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Objective: To investigate the feasibility and clinical significance of a continuous auscultation recorder of bowel sounds based on artificial intelligence in monitoring the bowel sounds. Methods: From November 1,2018 to August 12,2019, a continuous auscultation recorder of bowel sounds was applied to monitor the perioperative bowel sounds of 31 patients undergoing colorectal surgery, in order to discovery underlying rules which might be used to guide clinical practice. Results: After the operation, the bowel sounds continued to exist for (1.8±0.8) h, and then gradually weakened or disappeared, and recovered gradually after (11.2±3.5) h. The first exhaust and the first defecation were detected at the time of (22.7±5.8) h and (28.7±6.9) h after surgery, respectively. The bowel sounds rate increased after eating, and decreased significantly after exhaust/defecation. Conclusions: The continuous auscultation recorder of bowel sounds based on artificial intelligence was safe and effective, which can afford help to clinical evaluation.
Assuntos
Inteligência Artificial , Auscultação , Motilidade Gastrointestinal , Humanos , Monitorização FisiológicaRESUMO
Recently, exposure to air pollutants has been associated with the development and progression of systemic lupus erythematosus (SLE). The current study aims to evaluate the effects of air pollutants on SLE hospital admissions in Bengbu, China. We performed distributed lag non-linear model combined with quasi-Poisson generalized linear regression to assess the impacts of air pollutants on SLE admissions from 2015 to 2017. Subgroup analyses by admission status (first admission or readmission) were also evaluated. A total of 546 hospital admissions during 2015-2017 were included. For single-day lag structures, the risk effects occurred from lag 2 to lag 9 for the 75th percentile particulate matter (PM)2.5, lag 3 to lag 9 for the 80th percentile PM2.5. For cumulative lag structures, the risk effects occurred from lag 0-5 to lag 0-14 for both 75th PM2.5 and 80th PM2.5, and no significant effect was observed for 90th PM2.5. In addition, the adverse effects on SLE first admissions occurred from lag 0 to lag 1 for NO2, lag 1 to lag 2 for SO2. The maximum effect of PM2.5 on SLE was 4.27 (95% confidence interval: 1.34-13.59) at lag 0-13 day, the minimum effect value was 1.12 (95% confidence interval: 1.03-1.23) at lag 9 day. These findings demonstrate that high PM2.5, NO2 and SO2 are associated with SLE hospital admissions. In addition, this study further revealed that exposure to high concentration of PM2.5 increased the risk of SLE relapse, while high levels of NO2 and SO2 increased the risk of SLE first admissions.
Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Lúpus Eritematoso Sistêmico/epidemiologia , Adulto , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Exposição Ambiental/análise , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lúpus Eritematoso Sistêmico/etiologia , Masculino , Material Particulado/análise , Material Particulado/toxicidade , Fatores de Risco , Fatores de TempoRESUMO
OBJECTIVE: This study aims to investigate the plasma melatonin levels in systemic lupus erythematosus (SLE) patients and its relationship with clinical and laboratory features. PATIENTS AND METHODS: A total of 90 patients with SLE (82 females, 8 males; mean age 37.86 ± 13.98 years, range 19-77 years) and 90 healthy controls (82 females, 8 male; mean age 36.54 ± 10.89 years, range 22-60 years) were recruited for the current study. Plasma melatonin levels were detected by enzyme-linked immunosorbent assay. RESULTS: Melatonin levels were not significantly different in the plasma of patients with SLE compared with controls (P = 0.026). There was no significant difference regarding plasma melatonin level between SLE patients with nephritis and those without nephritis (P = 0.714); no significant difference was found between less active SLE and more active SLE (P = 0.791). The presence of IgM was associated with melatonin levels (P = 0.031) in SLE patients. CONCLUSIONS: There is no significant difference in plasma melatonin levels between SLE patients and controls. Further studies are needed to elucidate the role of melatonin in SLE.
Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Melatonina , Adulto , Idoso , Anticorpos Antinucleares , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Nefrite Lúpica/sangue , Masculino , Melatonina/sangue , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: In hypoxic conditions, miRNA-210 plays an important role in regulating the expression of hypoxia-inducing factor-1α (HIF-1α) and the differentiation of T helper 17 (Th17) cells, and this may be involved in the development and function of the immune system. AIMS: This study was to investigate the miR-210 expression levels in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and its association with the clinical and laboratory features of both diseases. METHODS: Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect miR-210 expression levels in PBMCs from 35 patients with SLE, 38 patients with RA, and 35 healthy controls. RESULTS: Compared with the healthy controls, the miR-210 expression levels were significantly increased in patients with SLE (P = 0.001) and there was increased significantly expression of miR-210 in SLE with pleuritis (Z = -2.345, P = 0.019) and anti-SSB/La-positive group (Z = -2.076, P = 0.038). However, we have not found the significant correlation between the miR-210 levels and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (r s = 0.091, P = 0.602). Although, no significant difference between miR-210 levels in RA patients and those in healthy controls was found (Z = -1.226, P = 0. 220). There was a significant decreased expression of miR-210 in active RA patients than inactive RA patients (Z = -4.011, P < 0.001). CONCLUSIONS: The dysregulation of miR-210 levels in SLE and RA patients suggests that miR-210 might play an important role in the pathogenesis of these diseases.
Assuntos
Artrite Reumatoide/genética , Leucócitos Mononucleares/metabolismo , Lúpus Eritematoso Sistêmico/genética , MicroRNAs/metabolismo , Adulto , Artrite Reumatoide/sangue , Artrite Reumatoide/metabolismo , Feminino , Humanos , Lúpus Eritematoso Sistêmico/metabolismo , MasculinoRESUMO
BACKGROUND: The IRAK1 and miR-499 polymorphisms play an important role in the etiology of rheumatoid arthritis (RA). Several studies have been carried out to estimate the association between IRAK1 rs3027898 and miR-499 rs3746444 and RA risk; however, the results were inconsistent. AIM: A case control study was carried out to explore the association between IRAK1 rs3027898 and miR-499 rs3746444 and the RA risk in a Chinese population. Meta-analyses combining present with previous studies were conducted to further explore the association. MATERIAL AND METHODS: A total of 386 RA patients were enrolled along with 576 matched healthy controls. Genotyping was performed by using TaqMan genotyping assays on Fluidigm 192.24 system. For the meta-analysis, a systematic literature search was conducted to identify all relevant studies. RESULTS: This case control study showed that the IRAK1 rs3027898 C allele was associated with increased risk of RA with an odds ratio (OR) = 1.4 and 95 % confidence intervals (CI) = 1.093-1.793, P = 0.008 but miR-499 rs3746444 polymorphisms were not significantly associated with the risk for RA. The meta-analyses included a total of 4 case control studies on IRAK1 rs3027898 and 4 studies on miR-499 rs3746444. The IRAK1 rs3027898 C allele had an overall OR of 1.268 (95 % CI = 1.130-1.424, P < 0.001). After stratification by ethnicity the C allele had an OR of 1.238 (95 % CI = 1.096-1.398, P = 0.001) in Asians. No association between miR-499 rs3746444 polymorphism and RA was found in the overall and Asian populations. CONCLUSION: The results from our case control study and the meta-analyses indicate that the IRAK1 rs3027898 C allele is significantly associated with an increased risk of RA, especially in Asians.
Assuntos
Alelos , Artrite Reumatoide/genética , Povo Asiático/genética , Quinases Associadas a Receptores de Interleucina-1/genética , MicroRNAs/genética , Polimorfismo Genético/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Risco , Transdução de Sinais/genéticaRESUMO
In order to determine whether tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene polymorphisms confers susceptibility to systemic lupus erythematosus (SLE) in ethnically different populations. A meta-analysis was conducted to examine the association between TNFAIP3 polymorphisms and susceptibility to SLE. A systematic literature search was conducted to identify all relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the association. A total of 23 studies from 20 articles, involving 18,501 patients with SLE and 30,435 healthy controls were included in this meta-analysis. Overall, we found significant association between SLE and the TNFAIP3 rs2230926, rs5029937, rs5029939, and rs3757173 polymorphisms (all P < 0.001). Stratification by ethnicity indicated that rs5029939 polymorphism was associated with SLE in Europeans, while rs2230926, rs5029937, and rs3757173 polymorphisms were associated with SLE both in Europeans and Asians (all P < 0.001). The results of our meta-analysis suggest that TNFAIP3 (rs2230926, rs5029937, rs5029939, and rs3757173) polymorphisms are associated with susceptibility to SLE.
Assuntos
Alelos , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética , Povo Asiático , Estudos de Casos e Controles , Expressão Gênica , Frequência do Gene , Genótipo , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Razão de Chances , Risco , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/imunologia , População BrancaRESUMO
This study aims to investigate the serum T-cell immunoglobulin mucin (TIM)-1 and TIM-3 levels in systemic lupus erythematosus (SLE) patients and analyze their correlations with clinical features. Sixtyone SLE patients and 69 healthy controls were enrolled, serum TIM-1 and TIM-3 levels were detected by ELISA. Results demonstrated that both serum TIM-1 and TIM-3 levels were significantly decreased in SLE patients compared with controls (both P less than 0.05). Lower serum TIM-3 levels in SLE patients with nephritis were observed when compared to those without nephritis, with a marginal statistical significance (P=0.059). However, both serum TIM-1 and TIM-3 levels had no significant correlation with SLE disease activity (both >0.05). In summary, decreased serum TIM-1 and TIM-3 levels and association of TIM-3 with nephritis suggest their possible role in the development and pathogenesis of SLE. However, further studies are needed to confirm these preliminary results.
Assuntos
Lúpus Eritematoso Sistêmico/sangue , Glicoproteínas de Membrana/sangue , Proteínas de Membrana/sangue , Receptores Virais/sangue , Adulto , Receptor Celular 1 do Vírus da Hepatite A , Receptor Celular 2 do Vírus da Hepatite A , Humanos , Lúpus Eritematoso Sistêmico/patologia , MasculinoRESUMO
Fruit ripening is a complex developmental process, the details of which remain largely unknown in fleshy fruits. In this paper, the fruit flesh of two peach varieties, "Zhongyou9" (a nectarine; Prunus persica L. Batsch) and its mutant "Hongyu", was analyzed by RNA-seq technology during two stages of ripening at 20-day intervals. One hundred and eighty significant upregulated and two hundred and thirty-five downregulated genes were identified in the experiment. Many of these genes were related to plant hormones, chlorophyll breakdown, accumulation of aroma and flavor volatiles, and stress. To the best of our knowledge, this is the first transcriptome analysis of peach ripening, and our data will be useful for further studies of the molecular basis of fruit ripening.
Assuntos
Frutas/genética , Perfilação da Expressão Gênica , Prunus persica/genética , Transcriptoma , Regulação da Expressão Gênica de Plantas , Mutação , Prunus persica/metabolismoRESUMO
Hand, foot and mouth disease (HFMD) is an acute contagious condition caused by a spectrum of human enteroviruses. HFMD reinfection is common in the absence of cross-protection from other virus subtypes. This study focused on reinfection in children in Anhui province, China between 2008 and 2013 using surveillance system data. We classified 8960 cases as reinfected, corresponding to a rate of 2·02%. The reinfection rate was higher in boys than in girls [odds ratio (OR) 1·27, 95% confidence interval (CI) 1·21-1·32, P < 0·001], children aged < 3 years (OR 3·82, 95% CI 3·58-4·07, P < 0·001), and children living in rural areas (OR 1·09, 95% CI 1·04-1·14, P = 0·001). The reinfection rate in children who were originally infected with non-enterovirus A71 (non-EVA71) enteroviruses was higher than those infected with EVA71 (OR 1·36, 95% CI 1·02-1·80, P = 0·034). Influential factors of reinfection rate included annual incidence (ß coefficient = 0·715, P = 0·002) and the proportion of EVA71 in patients with mild HFMD (ß coefficient = -0·509, P = 0·018). These results demonstrate that boys aged <3 years, especially those in rural areas or regions with a lower EVA71 proportion are more prone to reinfection, and specific health education programmes should be developed to protect these susceptible populations.
Assuntos
Enterovirus Humano A/fisiologia , Doença de Mão, Pé e Boca/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Doença de Mão, Pé e Boca/virologia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Fatores de RiscoRESUMO
OBJECTIVE: Studies investigating the association between interleukin (IL)-4 gene promoter -590C/T (rs2243250) polymorphism and autoimmune diseases report conflicting results. To derive a more precise estimation of the relationship, a meta-analysis was performed. METHODS: A systematic literature search was conducted to identify relevant studies. Pooled odds ratio (OR) with 95% confidence interval (CI) was used to estimate the strength of association. RESULTS: A total of 6001 cases and 6788 controls from 24 studies were analysed. Significant association of the C allele of IL-4 rs2243250 polymorphism with rheumatoid arthritis (RA) was detected (odds ratio (OR) = 0.696, 95% confidence interval (CI) = 0.601-0.807). Stratification by ethnicity indicated an association between the IL-4 rs2243250 polymorphism and RA in Caucasians. Furthermore, the overall ORs of the associations between the C allele and multiple scleorosis (MS) were 1.340 (95% CI = 1.102-1.630). However, we failed to reveal any association between IL-4 rs2243250 polymorphism and systemic lupus erythematosus (SLE), type 1 diabetes (T1D) or Graves' disease (GD). CONCLUSIONS: The present study suggests that the IL-4 rs2243250 polymorphism might be associated with genetic susceptibility to autoimmune diseases, including RA and MS.
Assuntos
Doenças Autoimunes/genética , Predisposição Genética para Doença , Interleucina-4/genética , Artrite Reumatoide/etnologia , Artrite Reumatoide/genética , Doenças Autoimunes/etnologia , Diabetes Mellitus Tipo 1/genética , Doença de Graves/etnologia , Doença de Graves/genética , Humanos , Lúpus Eritematoso Sistêmico/genética , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras GenéticasRESUMO
AIM: Published data regarding the association of leptin levels with rheumatoid arthritis (RA) are contradictory. To derive a more precise estimation of this relationship, a meta-analysis was performed. METHODS: Published literature from PubMed, Embase and Cochrane Library was obtained. Pooled standard mean difference (SMD) with 95 % confidence interval (CI) was calculated using fixed-effects or random-effect model analysis. Heterogeneity among studies was evaluated using the Cochran Q and I (2) statistics. The study quality was assessed by the Newcastle-Ottawa scale. RESULTS: A total of 20 studies including 998 RA patients and 692 controls were finally included in the meta-analysis. Compared to healthy controls, RA patients had significantly higher leptin levels (SMD 1.19, 95 % CI 0.59-1.79). Subgroup analyses showed that region, race, age, body mass index (BMI), disease duration and disease activity were positively associated with plasma leptin levels in RA patients. Sensitivity analysis showed no significant change when any one study was excluded. Publication bias was also undetected. CONCLUSIONS: The present meta-analysis suggested that leptin levels were higher in RA patients than those in healthy controls, which may be subject to different region, race, age, BMI, disease duration and disease activity.
Assuntos
Artrite Reumatoide/sangue , Leptina/sangue , Estudos de Casos e Controles , Estudos de Coortes , Estudos Transversais , HumanosRESUMO
OBJECTIVE: The objective of this paper is to examine some solid tumors incidence in patients with systemic lupus erythematosus (SLE) derived from population-based cohort studies by means of meta-analysis. METHODS: Relevant electronic databases were searched for studies characterizing the associated risk of overall malignancy and four site-specific malignancies (lung, liver, prostate, bladder cancer) in patients with SLE. The meta-analysis procedure was used to pool standardized incidence rates (SIRs) with 95% confidence intervals (CIs) to evaluate the association. RESULTS: A total of seven cohort studies were identified, of which six provided the SIR for overall malignancy, seven reported the SIR for lung cancer, five for liver cancer, four for prostate cancer and six for bladder cancer. Overall, lung and liver cancers were more frequently observed in patients with SLE with SIR of 1.16 (95% CI = 1.12-1.21), 1.68 (95% CI = 1.33-2.13) and 2.44 (95% CI = 1.46-4.05), respectively. However, the risk of prostate cancer appeared to be somewhat reduced in male patients with SLE (SIR = 0.71, 95% CI = 0.57-0.89). CONCLUSIONS: This meta-analysis shows that SLE patients are at increased risk of developing cancer, particularly of the lung, bladder and liver. However, males with SLE have a decreased risk of prostate cancer.
Assuntos
Neoplasias Hepáticas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Neoplasias da Próstata/epidemiologia , Neoplasias da Bexiga Urinária/epidemiologia , Feminino , Humanos , Incidência , Modelos Lineares , Neoplasias Hepáticas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Razão de Chances , Prognóstico , Neoplasias da Próstata/diagnóstico , Medição de Risco , Fatores de Risco , Fatores Sexuais , Neoplasias da Bexiga Urinária/diagnósticoRESUMO
BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by abnormal production of autoantibodies and proinflammatory cytokines. The clear pathogenesis of SLE has not been fully elucidated. Cytokine-mediated immunity has been showed to be involved in the pathogenesis of SLE. OBJECTIVES: The aim of this study was to investigate serum levels of cytokines (IL-19, IL-24, IL-26, IL-31, IL-32, IL-36) in SLE patients, in comparison with normal controls in a Chinese population. MATERIALS AND METHODS: A total of 65 patients with SLE and 65 healthy volunteers were recruited for the current study. All serum levels of cytokines were measured by enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Serum levels of IL-19, IL-24, IL-26, IL-31, IL-32 and IL-36 in SLE patients were not significantly different from the normal controls (all p > 0.05). CONCLUSION: Serum levels of IL-19, IL-24, IL-26, IL-31, IL-32 and IL-36 in SLE patients were not markedly different from the normal controls. However, functional research should be discussed in future studies to elucidate the roles of these cytokines in SLE.
Assuntos
Citocinas/sangue , Mediadores da Inflamação/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/epidemiologia , Adulto , Biomarcadores , China/epidemiologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Prevalência , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: The objective of this paper is to study the distribution regularity, development tendency and research hot spots of systemic lupus erythematosus (SLE) literature published in journals indexed in PubMed over a 10-year period using the bibliometric analysis method. METHODS: Citations from 2002 to 2011 were downloaded from the PubMed database. The core of the search was the Medical Subject Headings (MeSH) "Lupus Erythematosus, Systemic." The period of study was set from 2002 to 2011. RESULTS: A total of 14,053 articles were retrieved. These articles were published in 1627 different journals, nine journals contributing to one-third of all the literature. The first three journals containing the most articles were CONCLUSION: SLE has become a field of interest over the period 2002 to 2011. However, lupus research publications in developing countries have lagged behind.
Assuntos
Bibliometria , Pesquisa Biomédica/estatística & dados numéricos , Lúpus Eritematoso Sistêmico , Humanos , Medical Subject Headings , Publicações Periódicas como Assunto/estatística & dados numéricos , PubMed , Editoração/estatística & dados numéricosRESUMO
BACKGROUND: IgE plays a important role in systemic lupus erythematosus (SLE). A recent study identified the high-affinity IgE receptor α-chain (FcεRIα) gene FCER1A as a susceptibility locus influencing total serum IgE levels. AIM: To investigate whether the single-nucleotide polymorphism (SNP) rs2298804 (251 A>G) of FCER1A is associated with SLE and its clinical characteristics in a Chinese Han population. METHODS: This case-control study enrolled 948 patients with SLE and 976 healthy controls. Precise phenotyping of patients was accomplished by means of a questionnaire and clinical examination. rs2298804 was genotyped using real-time fluorescence quantitative PCR. RESULTS: Compared with the healthy controls, patients with SLE had much lower frequencies of the AG genotype (OR = 0.26; 95% CI 0.194-0.374; P << 0.001) and G allele (OR = 0.45; 95% CI 0.36-0.55; P << 0.001). We also found a stronger association of the FCER1A exon SNP, rs2298804 (A/G), in females (OR = 0.42; 95%CI 0.34-0.53; P << 0.001) compared with males (OR = 0.52; 95% CI 0.28-0.97; P < 0.04). G-allele carriers are less likely to develop SLE than A-allele carriers. Although we did not find any significant correlation between the rs2298804 and the incidence of lupus nephritis, rs2298804 seemed to protect against proteinunia, fever and hypocomplementaemia in patients with SLE, but appeared to be a risk factor for photosensitivity and vasculitis. CONCLUSIONS: We found that rs2298804 seemed to have a protective effect against SLE in Chinese patients, especially women. It also protected against proteinunia, fever and hypocomplementaemia, but was a risk factor for photosensitivity and vasculitis.
Assuntos
Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Receptores de IgE/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , China , Feminino , Frequência do Gene , Predisposição Genética para Doença/genética , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores Sexuais , Adulto JovemRESUMO
OBJECTIVE: The interleukin-10 (IL-10) gene polymorphism (-1082A/G) has been shown to be associated with systemic lupus erythematosus (SLE), but ï¬ndings are not consistent across studies. The aim of our meta-analysis was to assess the association between the -1082A/G polymorphism in the IL-10 gene and SLE. METHODS: We searched all publications on the association between the IL-10 (-1082A/G) polymorphism and SLE in PubMed, Elsevier Science Direct, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI) and Wanfang (Chinese). Meta-analysis was conducted using software Stata version 10.1. Meta-odds ratios (ORs) and 95% conï¬dence intervals (CIs) based on ï¬xed-/random-effects models depended on Cochran's Q-statistic and I(2) values. RESULTS: A total of 17 studies with 2396 cases and 3653 controls were included in this meta-analysis. Meta-analysis was performed for genotypes GG versus AA, GG + AG versus AA, GG versus AG + AA, and G allele versus A allele. Significant differences were found in genotype distribution between SLE and normal controls in whole-population GG versus AA (OR = 1.428, 95% CI = 1.006-2.208). Similar results were detected in the dominant genetics effect of the G allele (OR = 1.202, 95% CI = 1.030-1.403). No significant association was found in allele distribution in whole-population G versus A (OR = 1.125, 95% CI = 0.998-1.269). In subgroup analysis by ethnicity, significant association was found when GG + AG versus AA was performed in a European population (OR = 1.240, 95% CI = 1.022-1.503) and GG versus AG + AA was performed in an Asian population (OR = 3.596, 95% CI = 1.389-9.311). Significant association was found between genotype distribution in Asians (OR = 4.491, 95% CI = 1.552-13.000). Publication year was detected as the source of heterogeneity. In the stratified analysis by publication year, the pooled OR was 1.049 (95% CI = 0.940-1.171; P (heterogeneity) = 0.431; I(2) ( )= 0.4%) in subgroup 1 (publication years 1999-2004). No significant association was found between the IL-10 (-1082 G) allele and SLE in subgroup 1 (Z = 0.85, p = 0.431). In subgroup 2 (publication years 2005-2011), the pooled OR was 1.327 (95% CI = 1.125-1.565; P (heterogeneity) = 0.143; I(2) ( )= 35.8%). Significant association was found between the IL-10 (-1082 G) allele and SLE (Z = 3.36, p = 0.001). CONCLUSIONS: This meta-analysis demonstrates the association between the IL-10 (-1082A/G) polymorphism and SLE. However, further studies are needed for a definitive conclusion.
Assuntos
Interleucina-10/genética , Lúpus Eritematoso Sistêmico/genética , Humanos , Polimorfismo GenéticoRESUMO
Systemic lupus erythematosus (SLE) is the prototype of human autoimmune disease in which various inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1, IL-6 and interferon (IFN) play crucial pathogenic roles. The production of these cytokines is responsible for the mitogen-activated protein kinases (MAPKs), which can also generate mitogen-activated protein kinases phosphatases (MKPs). MKP-1, a prototypical member of the MKP family that can influence outcomes of autoimmune diseases and reduce the inflammatory cytokines by dephosphorylation of p38 and JNK MAPK, plays a critical role in the expression of inflammatory mediators at transcriptional and post-transcriptional levels. MicroRNA-101 (miR) is a small non-coding RNA that regulates the MAPK response by targeting MKP-1 mRNA 3'-UTR, and affects the secretion of the downstream inflammatory cytokines. However, the interaction among the above three in the pathogenesis of SLE has not previously been reported. This review discusses the current understanding of the role of the MAPK/MKP/miR-101 axis in regulating immune responses and the pathogenesis of SLE to provide new ideas for clinical treatment of SLE.
Assuntos
Fosfatase 1 de Especificidade Dupla/imunologia , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , MicroRNAs/imunologia , Proteínas Quinases Ativadas por Mitógeno/imunologia , Humanos , MicroRNAs/genéticaRESUMO
OBJECTIVES: To more precisely determine whether there is a significant association of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) gene polymorphisms with the susceptibility for Behçet's disease. METHODS: Eight studies that included data from 7 articles were identified using PubMed, Embase, Chinese Biomedical Literature Database (CBM), and Chinese National Knowledge Infrastructure (CNKI) published before March 2012. Meta-analysis was performed for two CTLA-4 gene polymorphisms, +49A/G (rs231775) and -318C/T (rs5742909). Statistical analyses were performed using software Review Manager (version 5.1) and Stata (version 11.0). The pooled odds ratio (OR) with 95% confidence interval (95%CI) were presented. RESULTS: Overall, no significant association was detected in all genetic models when all studies were pooled into the meta-analysis (for +49A/G polymorphism: A vs. G, OR=1.173, 95% CI=0.790-1.743; A/A vs. A/G+G/G, OR=1.422, 95% CI=0.718-2.814; A/A+A/G vs. G/G, OR=1.421, 95% CI=0.729-2.767; and for -318C/T polymorphism: C vs. T, OR=1.051, 95% CI=0.844-1.307; C/C vs. T/T+C/T, OR=1.154 95% CI=0.891-1.495, C/C+C/T vs. T/T, OR=1.044, 95% CI=0.301-3.617). Furthermore, in the subgroup analysis by ethnicity, there was also lack of evidence for the association in Turkish patients. CONCLUSIONS: Our study failed to provide evidence for the genetic association between CTLA-4 +49A/G and -318C/T polymorphisms with Behçet's disease based on currently available evidence from literature. Further confirmations in large and well-designed studies including other CTLA-4 gene polymorphisms are needed.
Assuntos
Síndrome de Behçet/genética , Antígeno CTLA-4/genética , Polimorfismo Genético , Síndrome de Behçet/imunologia , Frequência do Gene , Predisposição Genética para Doença , Humanos , Razão de Chances , Fenótipo , Medição de Risco , Fatores de RiscoRESUMO
OBJECTIVE: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. CD247 (CD3Z, TCRZ) plays a vital role in antigen recognition and signal transduction in antigen-specific immune responses, and is known to be involved in SLE pathogenesis. Weak disease association was reported for genetic variants in this gene in Caucasian studies for SLE, Crohn's disease and systemic sclerosis, but its role as a genetic risk factor was never firmly established. METHODS: In this study, using a collection of 612 SLE patients and 2193 controls of Chinese ethnicity living in Hong Kong in a genome-wide study, single nucleotide polymorphisms (SNPs) in and around CD247 were identified as being associated with SLE. The two most significant SNPs in this locus were selected for further replication using TaqMan genotyping assay in 3339 Asian patients from Hong Kong, Mainland China, and Thailand, as well as 4737 ethnically and geographically matched controls. RESULTS: The association of CD247 with SLE in Asian populations was confirmed (rs704853: odds ratio [OR] = 0. 81, p = 2.47 × 10(-7); rs858543: OR = 1.10, p = 0.0048). Patient-only analysis suggested that rs704853 is also linked to oral ulcers, hematologic disorders and anti-double-stranded DNA (dsDNA) antibody production. CONCLUSION: A significant association between variants in CD247 and SLE was demonstrated in Asian populations. Understanding the involvement of CD247 in SLE may shed new light on disease mechanisms and development of new treatment paradigms.