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Zhang Y.X.,Zhejiang University | Xue Y.,Zhejiang University | Xue Y.,Henan University of Science and Technology | Liu J.Y.,Zhejiang University | And 6 more authors.
Genetics and Molecular Research | Year: 2011

Toll-interleukin 1 receptor (TIR) domain containing adaptor protein (TIRAP; also known as MAL) is an essential adaptor molecule in Toll-like receptor signaling, involved in activating the innate immune response during infection. Genetic variations in the TIRAP gene may influence human susceptibility to infectious disease. To date, in the Chinese population, a possible predisposition of TIRAP gene variants to tuberculosis has not been reported. We investigated whether TIRAP gene polymorphisms are associated with the development of tuberculosis in a Chinese population. We investigated all the single-nucleotide polymorphisms (SNPs) within the TIRAP exon 5 in a case-control study of 212 patients with tuberculosis and 215 controls in a Chinese population. Genotyping was performed to identify the polymorphisms of TIRAP gene by PCR-DNA sequencing method. Haplotypes for the TIRAP gene variants were constructed using Haplo view version 4.2. Six polymorphisms of the SNPs listed in the National Center for Biotechnology Information database were detected in these Chinese tuberculosis patients. It was found that both the frequency of the 286A allele (odds ratio (OR) = 13.37; 95% confidence interval (CI) = 0.75-238.3; P < 0.01) and the frequency of 286AG genotype (OR = 13.57; 95%CI = 0.76-242.5; P < 0.01) were significantly higher in patients than in healthy controls. However, two other SNPs, C539T and C558T, reported to be associated with tuberculosis in other populations, were found not to be associated with tuberculosis in this Chinese population. We conclude that TIRAP G286A (D96N) polymorphism is associated with susceptibility to tuberculosis and may be a new risk factor for the development of tuberculosis in China. © FUNPEC-RP. Source


Wang C.,Zhejiang University | Liu C.-M.,Zhejiang University | Wei L.-L.,The Sixth Hospital of Shaoxing | Pan Z.-F.,The First Hospital of Jiaxing | And 6 more authors.
International Journal of Biological Sciences | Year: 2016

The epidemic of pulmonary tuberculosis (TB), especially multidrug-resistance tuberculosis (MDR-TB) presented a major challenge for TB treatment today. We performed iTRAQ labeling coupled with two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) and Solexa sequencing among MDR-TB patients, drug-sensitive tuberculosis (DS-TB) patients, and healthy controls. A total of 50 differentially expressed proteins and 43 differentially expressed miRNAs (fold change >1.50 or <0.60, P<0.05) were identified in the MDR-TB patients compared to both DS-TB patients and healthy controls. We found that 22.00% of differentially expressed proteins and 32.56% of differentially expressed miRNAs were related, and could construct a network mainly in complement and coagulation cascades. Significant differences in CD44 antigen (CD44), coagulation factor XI (F11), kininogen-1 (KNG1), miR-4433b-5p, miR-424-5p, and miR-199b-5p were found among MDR-TB patients, DS-TB patients and healthy controls (P<0.05) by enzyme-linked immunosorbent assay (ELISA) and SYBR green qRT-PCR validation. A strong negative correlation, consistent with the target gene prediction, was found between miR-199b-5p and KNG1 (r=-0.232, P=0.017). Moreover, we established the MDR-TB diagnostic model based on five biomarkers (CD44, KNG1, miR-4433b-5p, miR-424-5p, and miR-199b-5p). Our study proposes potential biomarkers for MDR-TB diagnosis, and also provides a new experimental basis to understand the pathogenesis of MDR-TB. © Ivyspring International Publisher. Source


Liu J.,Hangzhou Normal University | Jiang T.,Zhejiang University | Jiang F.,Beijing University of Chinese Medicine | Xu D.,Zhejiang University | And 5 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2015

A major challenge in pulmonary tuberculosis (TB) control is early and accurate diagnosis of sputum smear negative pulmonary TB (SSN-PTB). The patients with SSN-PTB have to wait for a longer period of time before receiving proper treatment than sputum smear positive pulmonary TB (SSP-PTB) patients due to delay in diagnosis. The purpose of this study is to discover potential serum protein biomarkers for SSN-PTB. Surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF MS) combined with weak cation exchange (WCX) magnetic beads was used to screen serum samples from SSN-PTB patients (N = 66), SSP-PTB patients (N = 49), and healthy volunteers (N = 80). The serum protein profiles were analyzed with Biomarker Wizard system. A classification model was established using Biomarker Pattern Software (BPS). Fifty-eight protein peaks were identified to exhibit significant differences between SSN-PTB, SSP-PTB and healthy control groups (P < 0.05), among which 6 peaks were found to be down-regulated, while 10 peaks were up-regulated gradually in the healthy control, SSN-PTB, and SSP-PTB groups. Twenty-three discriminating m/z peaks were detected between SSN-PTB patients and healthy controls (P < 0.01, Fold ≥ 1.5). The classification tree combined with three protein peaks (2747.0, 4480.0, and 9410.1 Da) could distinguish SSN-PTB patients from healthy controls with a sensitivity of 83.33% and a specificity of 82.50%. Early diagnosis of SSN-PTB disease is critical in order to reduce morbidity and mortality associated with TB. The study will help to clarify the role of differential proteins in the pathogenesis of TB. © 2015, Int J Clin Exp Med.All rights reserved. Source


Wang C.,Zhejiang University | Chen Z.-L.,Zhejiang University | Pan Z.-F.,The First Hospital of Jiaxing | Wei L.-L.,The Sixth Hospital of Shaoxing | And 6 more authors.
International Journal of Biological Sciences | Year: 2014

The association between NOD2 and tuberculosis (TB) risk has been reported widely, but the results of previous studies remained controversial and ambiguous. To assess the association between NOD2 polymorphisms and TB risk, a meta-analysis was performed. A literature search was conducted by using the PubMed, Ovid, ISI Web of Knowledge, Elsevier ScienceDirect, and Chinese National Knowledge Infrastructure (CNKI). We identified the data from all articles estimating the association between NOD2 polymorphisms and TB risk. In total, 2,215 cases and 1,491 controls in 7 case-control studies were included. In meta-analysis, we found significant association between the Arg702Trp polymorphism and TB risk (OR = 0.43, 95% CI = 0.20-0.90, P = 0.02). However, no significant association was found between the Arg587Arg (OR = 1.31, 95% CI = 0.83-2.07, P = 0.25) and Gly908Arg (OR = 0.78, 95% CI = 0.21-2.87, P = 0.71) polymorphisms and TB risk. The present meta-analysis suggested that NOD2 Arg702Trp polymorphism was likely to be a protective factor for TB. However, the Arg587Arg and Gly908Arg polymorphisms might not be the genetic risk factors for TB susceptibility. © Ivyspring International Publisher. Source


Xu D.-D.,Zhejiang University | Deng D.-F.,Zhejiang University | Li X.,Key Laboratory of Gastroenteropathy | Wei L.-L.,The Sixth Hospital of Shaoxing | And 12 more authors.
Proteomics | Year: 2014

Pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis is a chronic disease. Currently, there are no sufficiently validated biomarkers for early diagnosis of TB infection. In this study, a panel of potential serum biomarkers was identified between patients with pulmonary TB and healthy controls by using iTRAQ-coupled 2D LC-MS/MS technique. Among 100 differentially expressed proteins screened, 45 proteins were upregulated (>1.25-fold at p < 0.05) and 55 proteins were downregulated (<0.8-fold at p < 0.05) in the TB serum. Bioinformatics analysis revealed that the differentially expressed proteins were related to the response to stimulus, the metabolic and immune system processes. The significantly differential expression of apolipoprotein CII (APOCII), CD5 antigen-like (CD5L), hyaluronan-binding protein 2 (HABP2), and retinol-binding protein 4 (RBP4) was further confirmed using immunoblotting and ELISA analysis. By forward stepwise multivariate regression analysis, a panel of serum biomarkers including APOCII, CD5L, and RBP4 was obtained to form the disease diagnostic model. The receiver operation characteristic curve of the diagnostic model was 0.98 (sensitivity = 93.42%, specificity = 92.86%). In conclusion, APOCII, CD5L, HABP2, and RBP4 may be potential protein biomarkers of pulmonary TB. Our research provides useful data for early diagnosis of TB. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

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