TIM-3 gene is highly expressed in ephithelial ovarian cancer to promote proliferation and migration of ovarian cancer cells / 南方医科大学学报

OBJECTIVE@#To analyze the expression of immunoglobulin mucin molecule 3 (TIM-3) in epithelial ovarian cancer (EOC) and the effects of TIM-3 knockdown and overexpression on proliferation and migration of ovarian cancer cells.@*METHODS@#We analyzed TIM-3 expression in EOC and normal ovarian tissues using GEPIA database. We also detected TIM-3 expression levels in 82 surgical specimens of EOC and 18 specimens of normal ovarian tissues using immunohistochemistry, and analyzed the correlation of TIM-3 expression with clinicopathological parameters and survival outcomes of the patients. The expression of TIM-3 and Wnt1 mRNA in the tissues were detected using qRT-PCR. We constructed SKOV3 cell models of TIM-3 knockdown and overexpression and examined the changes in proliferation, apoptosis, migration and invasion of the cells using MTT assay, Annexin V-FITC/PI staining, scratch test and Transwell assay. The activity of Wnt/β-catenin pathway in the transfected was detected using dual luciferase reporter assay, and the mRNA levels of TCF-7, TCCFL-2 and CD44 were detected using qPCR. The protein expressions of MMP-9, CD44, Wnt1, β-catenin and E-cad in the transfected cells were detected with Western blotting.@*RESULTS@#The positive expression rate of TIM-3 was significantly higher in EOC tissues than in normal ovarian tissues (P < 0.05). The expression of TIM-3 was significantly correlated with FIGO stage, histological differentiation and lymph node metastasis, and was positively correlated with Wnt1 level (P < 0.05). In SKOV3 cells, TIM-3 knockdown significantly lowered the activity of Wnt/ β-catenin pathway, inhibited cell proliferation, migration and invasion, and promoted cell apoptosis. TIM-3 knockdown significantly down-regulated the mRNA levels of TCF-7, TCFL-2 and CD44 and the protein levels of MMP-9, CD44, Wnt1 and β-catenin, and significantly up-regulated the expression level of E-cad (P < 0.05). Overexpression of TIM-3 caused opposite effects in SKOV3 cells.@*CONCLUSION@#TIM-3 is highly expressed in EOC tissue to promote malignant behaviors of the tumor cells possibly by activating the Wnt/β-catenin signal pathway.

Research Progress in the Role of Tim3/galectin-9 in Hematological Malignancy--Review / 中国实验血液学杂志

The incidence of hematological malignant tumor is increasing year by year, and seriously affecting the human health. In addition to the traditional radiation and chemotherapy, immunotherapy has achieved a certain effect in the treatment of blood tumor, but it is limited by exhaustion of CD8

Exhaustion of CD8 / 中国实验血液学杂志

OBJECTIVE@#To investigate the changes in function of CD8@*METHODS@#Flow cytometry was used to detect the expressions of PD-1, TIM-3, and LAG-3, which were the markers of exhausted CD8@*RESULTS@#The expressions of inhibitory receptors (PD-1, TIM3 and LAG-3) on CD8@*CONCLUSION@#The exhausted CD8

Significance of Tim-3 in The Imbalance of Th17/Treg in Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the singnificance of Tim-3 in Th17/Treg balance in patients with multiple myeloma (MM).@*METHODS@#Fifty-six newly diagnosed MM patients and 30 healthy people were enrolled. Flow cytometry was used to detect the expression of Tim-3 on CD4@*RESULTS@#Compared with the control group, the expression of Tim-3 on CD4@*CONCLUSION@#The ratios of Th17/Treg, IL-17/IL-10 and Tim-3

Expression and Significance of PD-1, TIM-3 and VISTA on T Cell of Acute Myeloid Leukemia Patients / 中国实验血液学杂志

OBJECTIVE@#To study the expression of multiple negative costimulatory molecules on peripheral blood T cells in patients with acute myeloid leukemia (AML) and its affection on prognosis.@*METHODS@#The peripheral blood samples from patients with newly diagnosed AML, complete remission (CR), and no-remission (NR) were collected, the expression levels PD-1、VISTA and TIM-3 in CD4 and CD8 T cells were detected by flow cytometry , and the clinical data of patients were analyzed.@*RESULTS@#The expression levels of PD-1、VISTA and TIM-3 of CD4 and CD8 T cells in the newly diagnosed AML patients were significantly higher than those in control group (P＜0.05). The expression levels of PD-1、TIM-3 and VISTA of CD4 and CD8 T cells in the CR group were significantly lower than those in newly diagnosed and the NR group (P＜0.05). The TIM-3 expression level positively correlated with VISTA expression level of CD4 and CD8 T cells in newly diagnosed AML patients (r=0.85 and 0.73). The VISTA and PD-1 expression level of CD4 T cells in newly diagnosed AML, NR after first induction chemotherapy and high risk patients significantly increased (P＜0.05), the TIM-3 expression level of CD8 T cells in high risk group significantly increased (P＜0.05), and the VISTA expression level of CD8 T cells in CBFβ-MYH11 mutation-positive group significantly decreased (P＜0.05).@*CONCLUSION@#The expression of PD-1、TIM-3 and VISTA in AML peripheral blood T cells may be involved in the immune escape of AML and can be the targets of treatment for acute myeloid leukemia patients.

Correlation of the Expression Alteration of Tim-3 with the T Cell and B Cell Dysfunction in Peripheral Blood of Multiple Myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To study the correlation of the expression alteration of Tim-3 with the T cell and B cell dysfunction in peripheral blood of multiple myeloma (MM) patients.@*METHODS@#30 patients diagnosed as MM from October 2016 to October 2018 were selected and enrolled in MM group, and 30 healthy persons whose sex and age was matched with the MM patients were selected and enrolled in healthy control group (HC). The blood samples from MM patients and HC were collected, and the peripheral blood mononuclear cells (PBMNC) were separated by density gradient centrifugation, then the serum was kept for further study. The ratios of CD3CD4Tim-3T cells, CD3CD8Tim-3T cells and the CD19+CD20-CD38+B cells were analysed by flow cytometry (FCM)，and the concentration of T cell-related cytokines IFN-γ, TNF-αand B cell-related antibodies IgA, IgM and IgG were measured by ELISA. At the same time, the differences of the ratios of CCD3CD4Tim-3T, CD3CD8Tim-3T cells and plasmablast and the concentration of IFN-γ, TNF-α, IgA, IgM and IgG between the MM patient and HC were estimated, and the correlation of the ratio of CD3CD4Tim-3T, CD3CD8Tim-3T cells with the ratio of plasmablast and the concentration of IFN-γ, TNF-α, IgA, IgM and IgG in MM patients were analyzed.@*RESULTS@#The ratio of CD3CD4Tim-3T, CD3CD8Tim-3T cells increased in MM patients, while the ratio of CD19+CD20- CD38+B cells and the concentration of IFN-γ, TNF-α, IgA, IgM and IgG decreased in MM patients. And there was a negative correlation of the ratio of CD3CD4Tim-3T cells with CD19+CD20-CD38+B cells and the concentration of IFN-γ, IgA, IgM and IgG in MM patients, while the ratio of CD3CD8Tim-3T cells just negatively correlated with the concentration of TNF-α.@*CONCLUSION@#Expression of Tim-3 on CD4 and CD8 cells elevates in the peripheral blood of MM patients, which also correlates with the function suppression of T and B cells.

Expression of Costimulatory Molecule Tim3 on NK Cells and Its Subsets in Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of costimulatory molecule Tim3 and its subsets on NK cells in patients with acute myeloid leukemia.@*METHODS@#30 patients with acute myeloid leukemia treated in our hospital from August 2016 to August 2018 were randomly selected as the AML group, and 30 healthy persons in our hospital during the same period were randomly selected as the control group. The expression levels of CD56@*RESULTS@#The expression levels of CD56@*CONCLUSION@#The expression of costimulatory molecule Tim3 in NK cells and its subsets of patients with acute myeloid leukemia is down-regulated.

TIM-3 genetic variants and risk of Behçet disease in the Iranian population

Abstract: Background: Behçet disease is a prototypical systemic autoimmune disease, caused by a complex interplay between environmental and genetic factors. The transmembrane immunoglobulin and mucin domain-3 (TIM-3) is a distinct member of the TIM family that is preferentially expressed on Th1 cells and plays a role in Th1-mediated autoimmune or inflammatory diseases, such as Behçet disease. Objective: The aim of this study was to test the potential association between TIM-3 gene polymorphisms and Behçet disease. Methods: Two single-nucleotide polymorphisms of TIM-3 (rs9313439 and rs10515746) were genotyped in 212 patients with Behçet disease and 200 healthy controls. Typing of the polymorphisms was performed using multiplex PCR amplification. Results: There were no significant differences in allele and genotype frequencies between the Behçet disease patients and controls who were successfully genotyped. Similar results were also found after stratification by gender, age, or clinical features. Study limitations: Lack of studies on various racial or ethnic groups and small sample size. Conclusion: This study failed to demonstrate any association between the tested TIM-3 polymorphisms and Behçet disease.

Expression of CCR7 and Tim-3 in Childhood Patients with Acute Lymphoblastic Leukemia and Their Predictive Value for Prognosis / 中国实验血液学杂志

OBJECTIVE@#To analyze the expression of CCR7 and Tim-3 in childhood patients with acute lymphoblastic leukemia (ALL) and their predictive value for prognosis.@*METHODS@#Eighty-six newly diagnosed ALL childhood patients from January 2007 to January 2017 treated in our hospital were selected. The expression level of CCR7 and Tim-3 in bone marrow isolated cells of ALL patients were detected by flow cytometry, all the patients were divided into the recurrence group and non-recurrence group according to the follow-up results, the differences in the expressions of CCR7, Tim-3 between the two groups were compared. The correlation between the expression of CCR7 , Tim-3 and the clinicopathologic features of ALL patients were analyzed, the predictive value of CCR7 and Tim-3 for the prognosis of newly ALL patients were evaluated by ROC curve, and the relationship between serum CCR7, Tim-3 and prognosis were analyzed.@*RESULTS@#The expression levels of CCR7 and Tim-3 in recurrence group were significantly higher than those in non-recurrence group(P0.05). The exogenous infiltration rate of patients with high expression of CCR7 and Tim-3 was significantly higher than those in low expression group (P<005). The high expression rate 76.9% of Tim-3 in patients with T-ALL was significantly higher than that of B-ALL patients with Tim-3 high expression rate 45.2% (P<0.05). The median OS of patients with CCR7 level ≥45.97% and <45.97% were 9.3 months and 13.6 months respectively(P=0.004), and the Tim-3≥53.54% and Tim-3<53.54% were 9.1 months and 13.6 months respectively(P=0.001). The results of Cox's multi-factor regression analysis showed that CCR7 level(HR=1.024, 95 CI 1.001-1.049) and Tim-3 level (HR=1.879, 95 CI 1.183- 2.985) were the independent risk factors that affect the OS in ALL patients(P<0.05).@*CONCLUSION@#The expression of CCR7 and Tim-3 in bone marrow isolated cells of ALL patients shows good predictive value for prognosis, and the combination of CCR7 and Tim-3 can improve the sensitivity of the detection, the higher expression of CCR7 and Tim-3 can be used as potential indexes in prognosis evaluate.

Non-invasive messenger RNA transcriptional evaluation in human kidney allograft dysfunction

The aim of the present study was to evaluate messenger RNA expression in kidney allograft recipients. Forty-four kidney transplant recipients were evaluated up to three months after grafting. After transplantation, peripheral blood samples were drawn sequentially for real-time polymerase chain reaction analyses of perforin and TIM-3 genes. Biopsies were obtained to evaluate acute graft dysfunction and interpreted according to the Banff classification. Eight patients presented episodes of acute rejection. Recipients with rejection had significantly higher levels of TIM-3 mRNA transcripts compared to those without rejection (median gene expression 191.2 and 36.9 mRNA relative units, respectively; P<0.0001). Also, perforin gene expression was higher in patients with rejection (median gene expression 362.0 and 52.8 mRNA relative units; P<0.001). Receiver operating characteristic curves showed that the area under the curve (AUC) for the TIM-3 gene was 0.749 (95%CI: 0.670-0.827). Perforin gene mRNA expression provided an AUC of 0.699 (95%CI: 0.599 to 0.799). Overall accuracy of gene expression was 67.9% for the TIM-3 gene and 63.6% for the perforin gene. Combined accuracy was 76.8%. Negative predictive values were 95.3% for the TIM-3 gene, 95.5% for the perforin gene, and 95.4% in the combined analyses. Gene expression was significantly modulated by rejection treatment decreasing 64.1% (TIM-3) and 90.9% (perforin) compared to the median of pre-rejection samples. In conclusion, the longitudinal approach showed that gene profiling evaluation might be useful in ruling out the diagnosis of acute rejection and perhaps evaluating the efficacy of treatment.

Progress of molecular genetics research on rheumatoid arthritis / 中华医学遗传学杂志

Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disorder that principally attacks flexible joints and synovia. The precise pathogenesis of RA remains unclear, and genetic factors probably play an important role in its etiology. In addition to genes from human leukocyte antigen (HLA) region, such as HLA-DRB, genes from non-HLA region, such as TIM-3, PTPN22, TRAF1/C5, STAT4, CCR5, PADI4 and FCGR2A may also contribute to its susceptibility. The advance in molecular genetics research on RA is reviewed here.

TIM-1 acts a dual-attachment receptor for Ebolavirus by interacting directly with viral GP and the PS on the viral envelope

Ebolavirus can cause hemorrhagic fever in humans with a mortality rate of 50%-90%. Currently, no approved vaccines and antiviral therapies are available. Human TIM1 is considered as an attachment factor for EBOV, enhancing viral infection through interaction with PS located on the viral envelope. However, reasons underlying the preferable usage of hTIM-1, but not other PS binding receptors by filovirus, remain unknown. We firstly demonstrated a direct interaction between hTIM-1 and EBOV GP in vitro and determined the crystal structures of the Ig V domains of hTIM-1 and hTIM-4. The binding region in hTIM-1 to EBOV GP was mapped by chimeras and mutation assays, which were designed based on structural analysis. Pseudovirion infection assays performed using hTIM-1 and its homologs as well as point mutants verified the location of the GP binding site and the importance of EBOV GP-hTIM-1 interaction in EBOV cellular entry.

Up-regulated expression of Tim-3/Gal-9 at maternal-fetal interface in pregnant woman with recurrent spontaneous abortion / 华中科技大学学报（医学）（英德文版）

The relationship between T cell immunoglobulin domain and mucin domain protein 3 (Tim-3)/Galectin (Gal)-9 pathway and recurrent spontaneous abortion (RSA) was studied. Thirty-one pregnant women with RSA and 27 normal early gravidas were investigated to detect the levels of Tim-3 and Gal-9 in villi and deciduas by Western blotting. Meanwhile, the concentration of interleukin (IL)-4 and IL-12 in peripheral blood plasma was determined by ELISA in 25 healthy fertile non-pregnant controls, the normal early gravidas and pregnant women with RSA mentioned above, respectively. It was found that the relative expression levels of Tim-3 and Gal-9 in villi and deciduas were significantly increased in pregnant women with RSA as compared with those in the normal early gravidas. The concentration of IL-4 in peripheral blood plasma of pregnant women with RSA was lower than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05), but that of IL-2 in pregnant women with RSA was significantly higher than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05). It was suggested that the overexpression of Tim-3/Gal-9 pathway may be related to the pathogenesis of RSA.

Expression of TIM-1 and TIM-3 in spleen mononuclear cells and their role in Th1 polarization in primary immune thrombocytopenia patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the expression and clinical significance of T cell immunoglobulin mucin (TIM)-1, TIM-3 and T cell-specific transcription factors T-bet and GATA-3 in spleen mononuclear cells in patients with primary immune thrombocytopenia (ITP).</p><p><b>METHODS</b>The spleen samples were obtained from 17 active ITP patients and 10 controls with spleen traumatic rupture. By using real-time quantitative polymerase chain reaction, the mRNA expressions of TIM-3, TIM1, T-bet and GATA-3 were studied in all subjects.</p><p><b>RESULTS</b>TIM-3 mRNA levels of active ITP patients were significantly decreased to (29 ± 16)% of that of control, TIM-1 mRNA levels of active ITP patients increased to (3.20 ± 2.18) folds of that of control, but the difference was not significant. The ratio of TIM-1/ TIM-3 was elevated in active ITP patients. T-bet mRNA levels were up-regulated in ITP patients by (2.82 ± 1.57) folds (P<0.05) and the expression of GATA3 was decreased by 14% folds (P<0.05) compared to controls. The ratio of T-bet/GATA3 were significantly elevated in ITP patients.</p><p><b>CONCLUSION</b>The imbalance between TIM-3 and TIM-1 expression might play an important role in pathogenesis of ITP.</p>

Small hairpin RNA silencing Tim-3 affects peripheral blood Th1 and Th17 cells differentiation in asthmatic mice / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the effects of down-regulating Tim-3 gene in the peripheral blood mononuclear cells (PBMCs) of an asthmatic mouse model by short hairpin RNA (shRNA) and to explore the effect of Tim-3 on Th1 and Th17 cell differentiation.</p><p><b>METHODS</b>An asthmatic murine model was established by ovalbumin sensitization and challenge. PBMCs were isolated from asthmatic mice and transfected by shRNA targeting Tim-3 gene. The mRNA and protein expressions of Tim-3 were detected by quantitative PCR and Western blot. Flow cytometry analysis was performed to determine the levels of Th1 and Th17, and ELISA was performed to determine concentrations of IFN-γ, IL-4 and IL-17 in the supernatant.</p><p><b>RESULTS</b>Tim-3 mRNA expression in PBMCs was significantly increased in asthmatic mice. The mRNA and protein expression of Tim-3 decreased significantly in the shRNA group. Compared with the negative groups, Th1 cell levels increased and Th17 cell levels decreased significantly in the asthmatic groups after Tim-3 shRNA interference. In the Tim-3 shRNA interference groups concentrations of IFN-γ increased significantly while IL-17 decreased significantly.</p><p><b>CONCLUSIONS</b>Specific Tim-3 shRNA effectively silences the expression of Tim-3 and change in Tim-3 expression could affect T cell differentiation.</p>

Dexamethasone reduces IL-17 and Tim-3 expression in BALF of asthmatic mice / 华中科技大学学报（医学）（英德文版）

This study investigated the expression of interleukin-17 (IL-17) and T cell immunoglobulin mucin and domain-containing molecule-3 (Tim-3) in bronchoalveolar lavage fluid (BALF) of asthmatic mice and the effect of dexamethasone (DEX) on these factors. Thirty-six mice were randomly divided into three groups: normal group, asthmatic group and DEX group. The mouse model of asthma was established by sensitization with ovalbumin in both the asthmatic and DEX groups. The levels of IL-6, IL-10, IL-17 and TGF-β were measured in BALF by enzyme-linked immunesorbent assay (ELISA). The mRNA expression level of Tim-3 was detected by reverse transcription polymerase chain reaction (RT-PCR). The ratio of Tim-3+CD4+ cells to total CD4+ cells in BALF was determined by flow cytometry. Differential inflammatory cells in BALF were detected. The correlations among IL-17, IL-6, IL-10, Tim-3 and inflammatory cells were analyzed. The results showed that the levels of IL-17, IL-6 and Tim-3 were substantially increased and the IL-10 level decreased in BALF in the asthmatic mice, which was significantly reversed by DEX treatment. IL-17 expression was positively correlated with IL-6 and Tim-3 expression and the number of inflammatory cells but negatively with IL-10 expression. These results indicate that the increased expression of IL-17 and Tim-3 in BALF may be implicated in the occurrence and development of asthmatic inflammation; the mechanism by which DEX suppresses asthmatic airway inflammation involves down-regulation of IL-17 and Tim-3 levels.

Relationship between polymorphism sites of Tim-3 and allergic rhinitis in a population of Uigurs and Hans from Xinjiang Uigur Autonomous Region of China / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To find the relationship between the polymorphism of the Tim-3 gene mononucleotide site rs10515746 (-574G > T), rs4704853 (-882C > T), rs13170556, rs6555849 and the allergic rhinitis (AR) susceptibility in a population of Uigurs and Hans from Xinjiang Uigur Autonomous Region of China.</p><p><b>METHODS</b>The two mononucleotide polymorphism site of Uigur and Han AR patients and normal people were analyzed in Xinjiang in terms of SNaPshot SNP typing technique. The gene type and allelomorph frequency were than calculated. According to the Tim-3 gene layout, the gene type and the allelomorph frequency had been calculated. The Hardy-Weinberg balance law had been used for exam ination.</p><p><b>RESULTS</b>There were no statistic differences between the genotype and alleles of each frequency [site rs10515746(-574G > T), rs4704853 (-882C > T), rs13170556 and rs6555849)] of Uighurs, in group AR and matched group (all P > 0.05). There were no statistic differences between the genotype and alleles of each frequency of Han people in group AR and matched group (all P > 0.05). Except Han cases site rs4704853, the distribution of other genotype and alleles of each frequency accord with heredity balance through the Hardy-Weinberg balance law.</p><p><b>CONCLUSIONS</b>In Xinjiang Uigur autonomous region, locus of gene Tim-3, site rs10515746(-574G > T), rs4704853(-882C > T), rs13170556 and rs6555849, has the polymorphism of the Tim-3 gene mononucleotide. There is no correlation between AR susceptibility and Tim-3 gene mononucleotide site of Uigur people and Han people in Xinjiang.</p>

Expression of Galectin-9 and Tim-3 in lungs of mice with asthma / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the expression of Galectin-9 and Tim-3 in lungs of mice with asthma and the effect of rosiglitazone (PPAR-γ agonist) on their expression.</p><p><b>METHODS</b>Fortyfive BALB/c SPF female mice were randomized into control group and asthma groups with and without rosiglitazone intervention. After ovalbumin stimulation and rosiglitazone intervention the pathological changes of the lung tissues were observed. Galectin-9 and Tim-3 mRNA levels in lung tissues were determined using RT-PCR. The levels of IL-4 and IFN-γ in peripheral blood were measured using ELISA.</p><p><b>RESULTS</b>The expression of Galectin-9 and Tim-3 mRNA of lung tissues in the untreated asthma group increased significantly compared with the control and the rosiglitazone treated groups (P<0.05). A significantly increased blood expression of IL-4 and a significantly decreased blood expression of IFN-γ were found in the untreated asthma group compared with the control and the rosiglitazone-treated groups (P<0.05). The expression of Galectin-9 and Tim-3 mRNA was positively correlated with blood IL-4 level (r=0.792, r=0.794 respectively; P<0.05), but negatively correlated with blood IFN-γ level (r=-0.692, r=-0.757 respectively; P<0.05).</p><p><b>CONCLUSIONS</b>Galectin-9 and Tim-3 mRNA levels in lungs increase in mice with asthma and significantly correlate with the levels of blood Th1/Th2 cytokines. This suggests that Galectin-9 and Tim-3 are closely related to inflammatory process in asthma. Rosiglitazone treatment may decrease the expression of Galectin-9 and Tim-3.</p>

Linkage disequilibrium analysis of -1516, -574 and 4259 single nucleotide polymorphisms in TIM-3 gene / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the frequencies of -1516,-574 and 4259 single nucleotide polymorphisms (SNPs) of T cells immunoglobulin mucin -3(TIM-3) gene in Hubei population and address the question whether they are in linkage disequilibrium(LD) .</p><p><b>METHODS</b>Genotypes and allele frequencies of TIM-3 gene were examined by allele-specific polymerase chain reaction (AS-PCR) methods in 147 healthy Hubei Han individuals. Hardy-Weinberg equilibrium and Two-point LD analyses and haplotype frequencies were evaluated with Arlequin v3.1 software.</p><p><b>RESULTS</b>The allele frequencies of the 3 SNPs were in agreement with Hardy-Weinberg equilibrium. Minor allelic frequencies of TIM-3 -1516G/T,-574T/G and 4259G/T were 8.5%,1.0% and 2.0%,respectively. The dominant haplotypes comprising the three loci were G-G-G(2.0%),G-G-T(88.4%), T-G-T(8.5%) and G-T-T(1.0%). LD analyses revealed that all of the coefficient of linkage disequilibrium (D') were 1.</p><p><b>CONCLUSION</b>The -1516,-574 and 4259 loci of TIM-3 gene are in complete linkage disequilibrium. Our study has provided population genetic data on TIM-3 gene in Chinese Hubei Han population and a basis for searching immune-mediated disease-related TIM-3 haplotype.</p>

Study on relationship between polymorphism sites of TIM-3 and allergic asthma in a population of adult Hans from Hubei province of China / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate two single nucleotide polymorphism sites of the promoter region in T cells immunoglobulin domain and mucin domain protein-3 (TIM-3) and detect their relationship with allergic asthma in a population of adult Hans from Hubei province of China.</p><p><b>METHODS</b>The polymorphisms were detected with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allelic specific polymerase chain reaction (ASPCR). The genotype and allele frequencies were calculated and analyzed.</p><p><b>RESULTS</b>The genotype frequencies of CC, CT and TT in -1541 C/T polymorphism were 0.961, 0.039 and 0 respectively in the healthy population and were 0.935, 0.065 and 0 respectively in the allergic asthma population. No significant difference in genotype and alleles frequencies was found between the allergic asthma patients and control subjects (P=0.314, P=0.321). The genotype frequencies of GG, GT and TT in -574 T/G polymorphism were 0.992, 0.008 and 0 respectively in the healthy population and were 0.941, 0.059 and 0 respectively in the allergic asthma population. There was significant difference in genotype and allele frequencies between the allergic asthma patients and control subjects (P=0.046, P=0.048).</p><p><b>CONCLUSION</b>There are polymorphism sites of the promoter region in TIM-3 , and one of these sites, the -574 G/T polymorphism site, may be associated with allergic asthma in the population of adult Hans from Hubei province of China.</p>