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Objective To investigate the relationship between gene polymorphisms of T cell immunoglobulin domain and mucin domain protein-3 (Tim-3) and ulcerative colitis (UC) in Han nationality of Zhejiang.Methods A total of 391 UC patients and 573 healthy controls were recruited.Two single nucleotide polymorphisms (SPNs) of Tim-3 (rs1036199 and rs10515746) were examined by the improved multiple ligase detection reaction technique.Chi-square test or Fisher's exact test was performed to analyze the differences in the distribution of Tim-3 gene polymorphisms and its influence on the location and severity.Haploview 4.2 software was used to analyze linkage disequilibrium (LD) and haplotype.Results The frequencies of genotype CA+AA and mutant allele A of rs10515746 in UC were lower than those in healthy controls (1.79％,7/391 vs 4.19％,24/573;0.90％,7/782 vs 2.18％,25/1 146;x2=4.295 and 4.712,P=0.038 and 0.030).However,there was no significant differences in frequencies of genotype CA+ CC and mutant allele C of gene rs1036199 between UC patients and the healthy controls (1.79％,7/891 vs 8.49％,20/578;0.90％,7/782 vs 1.74％,20/1 146;both P＞0.05).The frequencies of genotype CA+AA and mutant allele A of rs10515746 in mild and moderate UC patients were both higher than those in severe UC patients (2.87 ％,7/244 vs 0;1.43 ％,7/488 vs 0),and the differences were statistically significant (Fisher's exact test,P=0.049 and 0.048).The analysis for LD indicated that rs1036199andrs10515746 were closeLD (D'=0.92,r2=0.72).Furthermore,the frequency of haplotype CA formed by the mutant alleles C and A of these two SNPs was lower in UC patients than that in healthy controls (0.64％,5/782 vs 1.74％,20/1 146),and the difference was statistically significant (x2 =4.441,P=0.035).Conclusions Tim-3 (rs10515746) gene mutation may not only decrease the incidence,but also reduce the severity of UC.Moreover,the haplotype CA formed by the mutant alleles of rs1036199 and rs10515746 may also reduce the incidence of UC.
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Objective To investigate the relationship between gene polymorphisms of T cell immunoglobulin domain and mucin domain protein-3 (Tim-3) and ulcerative colitis (UC) in Han nationality of Zhejiang.Methods A total of 391 UC patients and 573 healthy controls were recruited.Two single nucleotide polymorphisms (SPNs) of Tim-3 (rs1036199 and rs10515746) were examined by the improved multiple ligase detection reaction technique.Chi-square test or Fisher's exact test was performed to analyze the differences in the distribution of Tim-3 gene polymorphisms and its influence on the location and severity.Haploview 4.2 software was used to analyze linkage disequilibrium (LD) and haplotype.Results The frequencies of genotype CA+AA and mutant allele A of rs10515746 in UC were lower than those in healthy controls (1.79％,7/391 vs 4.19％,24/573;0.90％,7/782 vs 2.18％,25/1 146;x2=4.295 and 4.712,P=0.038 and 0.030).However,there was no significant differences in frequencies of genotype CA+ CC and mutant allele C of gene rs1036199 between UC patients and the healthy controls (1.79％,7/891 vs 8.49％,20/578;0.90％,7/782 vs 1.74％,20/1 146;both P＞0.05).The frequencies of genotype CA+AA and mutant allele A of rs10515746 in mild and moderate UC patients were both higher than those in severe UC patients (2.87 ％,7/244 vs 0;1.43 ％,7/488 vs 0),and the differences were statistically significant (Fisher's exact test,P=0.049 and 0.048).The analysis for LD indicated that rs1036199andrs10515746 were closeLD (D'=0.92,r2=0.72).Furthermore,the frequency of haplotype CA formed by the mutant alleles C and A of these two SNPs was lower in UC patients than that in healthy controls (0.64％,5/782 vs 1.74％,20/1 146),and the difference was statistically significant (x2 =4.441,P=0.035).Conclusions Tim-3 (rs10515746) gene mutation may not only decrease the incidence,but also reduce the severity of UC.Moreover,the haplotype CA formed by the mutant alleles of rs1036199 and rs10515746 may also reduce the incidence of UC.
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As an inhibitory receptor , T cell immunoglobulin mucin domain containing molecules-3 ( Tim-3 ) expresses high levels in the gastrointestinal tumor microenvironment .Tim-3 can promote T cell exhaustion , negatively regulate the anti-cancer immuni-ty of NK cell and induce polarization of macrophages to M 2.Tumor can escape from immunological surveillance through Tim-3.Tim-3 plays an important role in the development and transformation of gastrointestinal tumors .This article summarizes the role of Tim-3 in the gastrointestinal tumors from the aspects of gene polymorphism , T cells, NK cells and mononuclear macrophage .
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Objective To investigate the effect of down-regulating of T cell immunoglobulin domain and mucin domain protein-3 (Tim-3) gene in asthmatic mouse model by short hairpin RNA(shRNA) and explore the role of Tim-3 on the differentiation of helper T lymphocytes 17 (Thl7),airway inflammation,as well as airway hyperresponsiveness in pathogenesis of asthma.Methods An asthmatic murine model was established by way of ovalbumin (OVA) sensitization and challenge.Treating Tim-3 gene was intranasally administered with Tim-3-specific shRNA.Invasive pulmonary impedance method was adopted to detect mice airway resistance.Flow cytometry analysis was performed to determine the levels of Th17 ; enzyme linked immunosorbent assay was performed to determine the concentrations of IL-17 and transforming growth factor-beta(TGF-β) in supematant.Results Asthmatic mice model was successfully established.By using Tim-3 shRNA silencing Tim-3,airway inflammation was reduced and airway hyperresponsiveness was declined in asthmatic group ;the levels of Th17 cells in asthmatic group [(6.43 ± 1.01)％] were significantly increased compared with normal controls[(1.75 ± 0.02) ％].After using Tim-3 shRNA silencing Tim-3,the levels of Th17 cells [(2.36 ± 0.28) ％] were decreased (F =40.05,P ＜ 0.05) ; the level of IL-17 in asthmatic group [(118.8 ± 16.5) ng/L] was significantly increased compared with normal controls[(72.5 ± 13.6)ng/L],after using Tim-3 shRNA silencing Tim-3,the level of IL-17 [(73.6 ± 12.5) ng/L] was decreased (F =32.80,P ＜ 0.05),while the expression of TGF-β did not change.Conclusions Down regulation of Tim-3 gene can decrease airway inflammation and airway hyperresponsiveness,which may be related to the change of Th17 cell differentiation.