OBJECTIVE: To assess the association of microribonucleic acid (miRNA) gene polymorphisms with the risk and clinicopathological characteristics of Crohn's disease (CD) and the influence of miRNA gene variants on the response to ustekinumab (UST) treatment among CD patients. METHODS: From January 2018 to February 2025, 312 patients diagnosed with CD and 527 gender- and age-matched normal controls were selected as the study subjects at the Department of Gastroenterology of the Second Affiliated Hospital of Wenzhou Medical University. Genotypes of miR-155 (rs767649), miR-21 (rs13137), miR-124 (rs531564) and miR-146a (rs57095329, rs2431697) were determined with multiplex polymerase chain reaction-ligase detection reaction (PCR-LDR) technique. The patients were divided into different subgroups according to the Montreal Classification Criteria for CD. Harvey-Bradshaw index (HBI) and simplified endoscopic score for CD were respectively applied to assess the clinical and endoscopic disease activity of CD. Unconditional logistic regression model was employed to analyze the distribution of miRNA gene polymorphisms between the two groups, as well as their influence on the clinicopathological characteristics of CD patients. Among them, 185 CD patients received first-line UST treatment, with the first sufficient dose of UST (6 mg/kg) administered intravenously. Based on the changes in HBI at week 8, the response of patients to UST treatment was evaluated. Unconditional logistic regression model was employed to analyze the distribution of miRNA gene polymorphisms between clinically responsive group (the decline of HBI ≥ 3 scores compared to week 0) and non-responsive group. All of the P values were adjusted by Bonferroni correction. This study has been approved by the Medical Ethics Committee of the Second Affiliated Hospital of Wenzhou Medical University (Ethics No.: 2025-K-12-01). RESULTS: No significant difference was found in the distribution of miRNA gene polymorphisms between the two groups (all P > 0.05). The variant genotype (TC+CC) of rs2431697 was more common among patients with terminal ileal-type and ileocolic-type CD than those with the colonic-type CD (OR = 4.98, 95%CI: 1.49~16.68, P = 0.009, adjusted P = 0.045). However, the opposite conclusion was drawn for the homozygous variant genotype (TT) of rs13137 and variant genotype (GC+CC) of rs531564 (OR = 0.37, 95%CI: 0.18~0.76, P = 0.007, adjusted P = 0.035; OR = 0.36, 95%CI: 0.18~0.73, P = 0.004, adjusted P = 0.020). Compared to patients with non-stricturing and penetrating CD, the variant genotype (AG+GG) and variant allele (G) of rs57095329 were more common in those with stricturing and penetrating CD (OR = 4.06, 95%CI: 2.46~6.71, P < 0.001, adjusted P < 0.005; OR = 3.12, 95%CI: 2.06~4.73, P < 0.001, adjusted P < 0.005). However, the frequencies of variant genotype (AT+TT) and variant allele (T) of rs13137 were lower among patients with stricturing and penetrating CD than in those without (OR = 0.25, 95%CI: 0.15~0.41, P < 0.001, adjusted P < 0.005; OR = 0.45, 95%CI: 0.33~0.63, P < 0.001, adjusted P < 0.005). Additionally, the variant genotype (AG+GG) and variant allele (G) of rs57095329 were more common among those with moderately to severely endoscopic activity than those with mildly endoscopic activity (OR = 2.01, 95%CI: 1.19~3.42, P = 0.009, adjusted P = 0.045; OR = 2.04, 95%CI: 1.28~3.25, P = 0.003, adjusted P = 0.015). In total 117 cases had shown clinical response by week 8, while 68 cases showed no response. Compared with t he clinically non-responsive group, the variant genotype (TC+CC) and variant allele (C) of rs2431697 were more common in the clinically responsive group (OR = 3.86, 95%CI: 1.80~8.32, P = 0.001, adjusted P = 0.005; OR = 2.60, 95%CI: 1.34~5.06, P = 0.005, adjusted P = 0.025). However, the variant genotype (TA+AA) of rs767649 was less frequent in the clinically responsive group than the non-responsive group (OR = 0.40, 95%CI: 0.21~0.74, P = 0.004, adjusted P = 0.020). The same conclusion was drawn for the variant genotype (AT+TT) and variant allele (T) of rs13137 when the clinically responsive group was compared with the non-responsive group (OR = 0.30, 95%CI: 0.14~0.63, P = 0.002, adjusted P = 0.010; OR = 0.54, 95%CI: 0.35~0.82, P = 0.005, adjusted P = 0.025). CONCLUSION Genetic polymorphisms of miRNAs are not associated with the risk of developing CD. The miR-146a (rs57095329) variant may increase the endoscopic activity of CD and the risk for stenosis or penetration. However, the miR-146a (rs2431697) variant may increase the risk of ileal involvement. The miR-21 (rs13137) variant may reduce the risk of ileal involvement and the risk of stenosis or penetration. The miR-124 (rs531564) variant may reduce the risk of ileal involvement. Among patients receiving UST treatment, the miR-146a (rs2431697) variant may increase the clinical response by week 8. However, both the miR-155 (rs767649) and miR-21 (rs13137) variants may decrease the clinical response by week 8.
Humans ; MicroRNAs/genetics* ; Crohn Disease/pathology* ; Male ; Female ; Adult ; Polymorphism, Single Nucleotide ; Middle Aged ; Asian People/genetics* ; Genetic Predisposition to Disease ; Genotype ; Young Adult ; Case-Control Studies ; Adolescent ; East Asian People

Objective:To retrospectively analyze the effects of vitamin D supplementation on the clinical efficacy of ustekinumab (UST) in treatment of patients with Crohn′s disease (CD).Methods:Seventy-one patients with moderate to severe active CD who received the first-line treatment UST from May 2021 to February 2023 were collected by searching the clinical database of the Second Affiliated Hospital of Wenzhou Medical University. The disease activity of CD was evaluated by Harvey-Bradshaw index (HBI) and intestinal inflammation was assessed by simplified endoscopic score for Crohn′s disease (SES-CD). The CD patients were divided into supplementary group ( n=41) and non-supplementary group ( n=30) based on whether vitamin D supplementation (400 U/d) was performed during UST treatment. According to the baseline serum 25 (OH) D level, the patients were divided into vitamin D deficiency group (<20 μg/L, n=42) and non-deficiency group (≥20 μg/L, n=29). The main end points were the differences in the clinical remission (HBI score ≤4) rate and mucosal healing (SES-CD score ≤2) rate between supplementary group and non-supplementary group at week 24 of UST treatment. The secondary end points were the differences in the clinical response (the reduction of HBI score ≥3 compared to week 0) rate and biochemical remission (C-reactive protein (CRP)≤5 mg/L) rate between supplementary group and non-supplementary group at week 8 of UST treatment. A multiple linear regression analysis was performed to investigate the relation between serum 25(OH) D levels and the clinicopathological characteristics of CD patients. Multivariate binary logistic regression models were used to analyze the factors affecting the clinical efficacy of UST at week 8 and 24. Independent sample t test, Mann-Whitney U test, Chi-square test and Fisher′s exact test were used for comparisons between the two groups. Paired t test was used to analyze the differences before and after UST treatment. Results:The results of multiple linear regression analysis for 71 CD patients showed that the baseline serum 25(OH)D level was independent influencing factor for the baseline CRP level ( β=-0.33, 95% confidence interval (95% CI) -0.41 to -0.08, P=0.041) and baseline HBI score ( β= -0.52, 95% CI -0.68 to -0.33, P=0.027). Compared with week 0, the serum 25(OH)D level of supplementary group increased at week 8 ((17.18±5.46) μg/L vs. (13.71±7.73) μg/L), and the difference was statistically significant ( t=-7.81, P<0.001), however, there was no significant difference of serum 25(OH)D in non-supplementary group ((14.85±3.92) μg/L vs. (15.69±5.48) μg/L, P>0.05). At week 8, the HBI score and median CRP level of supplementary group were both lower than those of non-supplementary group (5.71±1.88 vs. 8.34±2.27, 10.83 mg/L (3.95 mg/L, 21.07 mg/L) vs. 16.17 mg/L (6.91 mg/L, 35.48 mg/L)), and the diffierences were statistically significant ( t=0.48, Z=2.87; P<0.001 and =0.001). However, the clinical response rate and biochemical remission rate were both higher than those of non-supplementary group (68.3%, 28/41 vs. 40.00%, 12/30 and 43.9%, 18/41 vs. 13.3%, 4/30), and the differences were statistically significant ( χ2=5.64 and 6.21, P=0.018 and 0.013). Compared with week 0, the serum 25(OH)D level of supplementary group increased ((24.73±8.34) μg/L) at week 24, and the difference was statistically significant ( t=-6.83, P<0.001), however, there was no statistically significant difference in the serum 25(OH)D level of non-supplementary group ((15.59±7.24) μg/L vs. (15.69±5.48) μg/L, P>0.05). At week 24, the decrease of HBI score and SES-CD score of supplementary group were both greater than those of non-supplementary group (difference between week 24 and week 0 -8.96±1.45 vs. -5.33±0.59, -7.00(-10.00, -3.00) vs. -2.00(-2.50, -1.50), and the differences were statisticalcy significant ( t=-5.64 and Z=-3.27, P<0.001 and =0.039). Moreover, the clinical remission rate and mucosal healing rate were both higher than those of non-supplementary group (65.9%, 27/41 vs. 26.7%, 8/30, and 61.0%, 25/41 vs. 30.0%, 9/30), and the differences were statistically significant ( χ2=10.64 and 6.66, P=0.001 and 0.010). At week 24, the analysis of non-supplementary group indicated that the clinical remission rate and mucosal healing rate of patients received vitamin D supplementary therapy were both higher than those of patients without vitamin D supplementary therapy (69.0%, 20/29 vs. 3/13, and 58.6%, 17/29 vs. 2/13), and the differences were statistically significant ( χ2=4.43 and 5.14, P=0.035 and 0.023). Vitamin D supplementing therapy was an independent influencing factor of clinical response rate and biochemical remission rate at week 8, clinical remission rate and mucosal healing rate at week 24 for UST treatment of CD ( OR(95% CI) were 5.83(1.15 to 7.59), 4.91(3.67 to 6.98), 5.13(2.88 to 9.44), 7.01(1.16 to 20.97), respectively; P<0.001, <0.001, <0.001, =0.036). Conclusion:Vitamin D supplementation may help to improve the clinical efficacy of UST treatment in CD patients, especially in patients with vitamin D deficiency.

Objective:To retrospectively analyze the effects of vitamin D3 supplementation on clinical remission of patients with Crohn′s disease (CD) in the treatment of infliximab (IFX).Methods:From January 2014 to January 2020, 73 patients with initial moderate to severe CD (50 patients with vitamin D deficiency (the level of serum 25-hydroxyvitamin D (25(OH)D)<50 nmol/L)) receiving IFX treatment at Department of Gastroenterology were screened from the clinical database of the Second Affiliated Hospital of Wenzhou Medical University. Harvey-Bradshaw index (HBI) was applied to evaluate the disease activity of CD patients. All the patients underwent IFX treatment (5 mg/kg) for at least 54 weeks. According to whether vitamin D3 (125 U/d) was supplemented during IFX treatment, the patients were divided into supplemented group ( n=37) and non-supplemented group ( n=36). In supplemented group, the level of 25(OH) D of patients at the 54th week was compared with that before IFX treatment. At the 54th week, the clinical remission rate and decline range of HBI were compared between supplemented group and non-supplemented group. And the influencing factors of clinical remission rate were analyzed in CD patients. Paired t test, independent sample t test, chi-square test and multivariable logistic regression were used for statistical analysis. Results:In supplemented group, the level of serum 25(OH)D at the 54th week was higher than that before IFX treatment ((50.83±15.45) nmol/L vs. (37.68±16.75) nmol/L), and the difference was statistically significant ( t=-4.55, P<0.001). At the 54th week, the clinical remission rate of supplemented group was higher than that of non-supplemented group (83.8%, 31/37 vs. 61.1%, 22/36), the decline range of HBI was larger than that of non-supplemented group (7.41±3.00 vs. 6.28±2.75), and the differences were statistically significant ( χ2=4.71, t=2.41; P=0.030 and 0.023). The results of multivariable logistic regression analysis showed that vitamin D3 supplementation was an independent factor affecting the clinical remission rate in CD patients ( n=73) and the patients with vitamin D deficiency ( n=50) ( b= -1.67 and -1.92 , P=0.015 and 0.019). Conclusions:Vitamin D3 supplementation can significantly improve the clinical remission rate in CD patients with IFX treatment, especially in CD patients with vitamin D deficiency.

Objects:To explore the association of colonic vitamin D receptor (VDR) expressionwith imbalance of Th17/regulatory T cells (Tregs) in patients with ulcerative colitis (UC) .Methods:The specimens of peripheral blood and colonic tissue were retrospectively collected from 30 UC patients and 15 controls (colonic polypadenoma) , respectively. The clinical data of all the participants were simultaneously recorded, including age, gender, smoking, body mass index, UC activity (assessed by Mayo scoring system) . The electrochemiluminescence method was conducted to measure the serum level of 25-hydroxyvitamin D [25 (OH) D]. Moreover, the immunohistochemical staining method was applied for examining the protein expression levels of VDR, Th17 and Treg cells related factors (RORγt, IL-17, Foxp3, IL-10, respectively) in the colonic tissues.Results:Compared with the controls, the expressions of RORγt, IL-17, Foxp3 and IL-10, together with the ratio of RORγt/Foxp3, were significantly higher in UC patients [0.32 (0.20, 0.46) ×10 -2 vs. 0.17 (0.11, 0.19) ×10 -2, 0.56 (0.30, 0.76) ×10 -2 vs. 0.19 (0.16, 0.26) ×10 -2, 0.26 (0.16, 0.33) ×10 -2 vs. 0.18 (0.12, 0.21) ×10 -2, 0.29 (0.19, 0.37) ×10 -2 vs. 0.06 (0.04, 0.09) ×10 -2, 1.14 (0.81, 1.86) vs. 0.86 (0.78, 0.92) , all P<0.05], meanwhile the expressions of RORγt, IL-17, Foxp3, IL-10, and the ratio of RORγt/Foxp3 were higher in patients with active UC than inactive UC [0.45 (0.31, 0.53) ×10 -2 vs. 0.16 (0.13, 0.20) ×10 -2, 0.73 (0.56, 0.78) ×10 -2 vs. 0.26 (0.21, 0.33) ×10 -2, 0.26 (0.24, 0.35) ×10 -2 vs. 0.17 (0.14, 0.26) ×10 -2, 0.35 (0.28, 0.38) ×10 -2 vs. 0.16 (0.11, 0.20) ×10 -2, 1.77 (0.90, 2.07) vs. 82.84 (64.12, 112.67) , all P<0.05]. The colonic VDR expression in UC patients was significantly lower than that in controls [0.66 (0.28, 19.15) ×10 -2 vs. 2.94 (2.61, 3.21) ×10 -2, P<0.001], meanwhile VDR expression was also shown to be lower in patients with active UC than that in those with inactive UC [0.37 (0.26, 0.69) ×10 -2 vs. 2.63 (1.78, 3.24) ×10 -2, P<0.001]. The subsequent linear regression analysis suggested that the ratio of RORγt/Foxp3 in colonic tissue of UC patients was independently and negatively associated to the colonic VDR expression ( β = -0.530, P = 0.003) . Conclusion:The lower colonic VDR expression is associated to the imbalance of Th17/Treg cells in UC patients.

Objects:To explore the association of colonic vitamin D receptor (VDR) expressionwith imbalance of Th17/regulatory T cells (Tregs) in patients with ulcerative colitis (UC) .Methods:The specimens of peripheral blood and colonic tissue were retrospectively collected from 30 UC patients and 15 controls (colonic polypadenoma) , respectively. The clinical data of all the participants were simultaneously recorded, including age, gender, smoking, body mass index, UC activity (assessed by Mayo scoring system) . The electrochemiluminescence method was conducted to measure the serum level of 25-hydroxyvitamin D [25 (OH) D]. Moreover, the immunohistochemical staining method was applied for examining the protein expression levels of VDR, Th17 and Treg cells related factors (RORγt, IL-17, Foxp3, IL-10, respectively) in the colonic tissues.Results:Compared with the controls, the expressions of RORγt, IL-17, Foxp3 and IL-10, together with the ratio of RORγt/Foxp3, were significantly higher in UC patients [0.32 (0.20, 0.46) ×10 -2 vs. 0.17 (0.11, 0.19) ×10 -2, 0.56 (0.30, 0.76) ×10 -2 vs. 0.19 (0.16, 0.26) ×10 -2, 0.26 (0.16, 0.33) ×10 -2 vs. 0.18 (0.12, 0.21) ×10 -2, 0.29 (0.19, 0.37) ×10 -2 vs. 0.06 (0.04, 0.09) ×10 -2, 1.14 (0.81, 1.86) vs. 0.86 (0.78, 0.92) , all P<0.05], meanwhile the expressions of RORγt, IL-17, Foxp3, IL-10, and the ratio of RORγt/Foxp3 were higher in patients with active UC than inactive UC [0.45 (0.31, 0.53) ×10 -2 vs. 0.16 (0.13, 0.20) ×10 -2, 0.73 (0.56, 0.78) ×10 -2 vs. 0.26 (0.21, 0.33) ×10 -2, 0.26 (0.24, 0.35) ×10 -2 vs. 0.17 (0.14, 0.26) ×10 -2, 0.35 (0.28, 0.38) ×10 -2 vs. 0.16 (0.11, 0.20) ×10 -2, 1.77 (0.90, 2.07) vs. 82.84 (64.12, 112.67) , all P<0.05]. The colonic VDR expression in UC patients was significantly lower than that in controls [0.66 (0.28, 19.15) ×10 -2 vs. 2.94 (2.61, 3.21) ×10 -2, P<0.001], meanwhile VDR expression was also shown to be lower in patients with active UC than that in those with inactive UC [0.37 (0.26, 0.69) ×10 -2 vs. 2.63 (1.78, 3.24) ×10 -2, P<0.001]. The subsequent linear regression analysis suggested that the ratio of RORγt/Foxp3 in colonic tissue of UC patients was independently and negatively associated to the colonic VDR expression ( β = -0.530, P = 0.003) . Conclusion:The lower colonic VDR expression is associated to the imbalance of Th17/Treg cells in UC patients.

Objective To investigate the correlation between decoy receptor (DcR) 1,DcR2,osteoprotegerin (OPG) gene polymorphisms and susceptibility of Crohn's disease (CD) in Han population in Zhejiang province.Methods From April 2008 to July 2017,at the Department of Gastroenterology of The Second Affiliated Hospital of Wenzhou Medical University,The First Affiliated Hospital of Wenzhou Medical University,Central Hospital of Wenzhou and Renmin Hospital of Wenzhou,285 patients diagnosed as having CD were enrolled,and during the same period 572 healthy individuals who received health checkup at the Second Affiliated Hospital of Wenzhou Medical University were collected as healthy control.The single nucleotide polymorphism (SNP) of DcR1 (rs12549481),DcR2 (rs1133782) and OPG (rs3102735) were examined by SNaPshot technique.An unconditional logistic regression analysis was performed to analyze the differences in each SNP mutation alleles and genotype frequencies between CD group and control group.Furthermore,their correlation with clinicopathological features of CD and the efficacy of corticosteroid and infliximab was also evaluated.Results The frequencies of mutant allele A and genotype GA + AA of DcR2 (rs1133782) of CD group were 11.93％ (68/570) and 22.81％ (65/285),respectively,which were higher than those of healthy control group (8.22％,94/1 144;and 15.91％,91/572;odds ratio (OR) =1.513,95％ confidence interval (CI) 1.088 to 2.104,P =0.013;OR =1.562,95％ CI 1.094 to 2.230,P =0.014).However there was no statistically significant difference in the mutant allele and genotype frequencies of DcR1 (rs12549481) and OPG (rs3102735) between two groups (all P ＞ 0.05).The frequencies of mutant allele C and genotype TC + CC of DcR1 (rs12549481) in patients with stricturing CD were 13.89％ (25/180)and 27.78％ (25/90),respectively,which were lower than those of patients with non-stricturing,non-penetrating CD (27.68％,62/224 and 48.21％,54/112),and the differences were statistically significant (OR =0.421,95％ CI 0.252 to 0.705,P =0.001;OR =0.413,95％ CI 0.229 to 0.747,P =0.003).Besides,the frequencies of mutant allele A and genotypes GA + AA of DcR2 in patients with penetrating CD were 7.23％ (12/166) and 13.25％ (11/83),which were lower than those of patients with non-stricturing,non-penetrating CD (15.62％,35/224 and 30.36％,34/112),and the differences were statistically significant (OR =0.407,95％ CI 0.205 to 0.809,P =0.009;OR =0.350,95％ CI 0.165 to 0.743,P =0.005).In addition,there was no statistically significant difference in the frequencies of mutant allele and genotypes of OPG (rs3102735) among subtypes of CD with different features (all P ＞ 0.012 5).Moreover,the DcR1 (rs12549481),DcR2 (rs1133782) and OPG (rs3102735) polymorphisms were not correlated with the efficacy of corticosteroid and infliximab (all P ＞ 0.05).Conclusions DcR1 (rs12549481) mutation may be correlated with stricturing CD.DcR2 (rs1133782) mutation may be correlated with CD,especially with penetrating CD.However,the gene polymorphism of OPG (rs3102735) is not correlated with the risk of CD susceptibility.And the above gene SNP may be independent of the efficacy of corticosteroid and infliximab.

Objective To explore the association of genetic polymorphism of fucosyltransferase (FUT) 2 and FUT3 and expression of Lewis antigen with ulcerative colitis (UC) in Chinese Zhejiang Han population.Methods We genotyped FUT2 (rs281377, rs1047781 and rs601338) and FUT3 (rs28362459, rs3745635 and rs3894326) in 485 UC patients and 580 healthy controls using SNaPshot. By immunohistochemistry method, we also evaluated expression of Lewis a and b antigens in the sigmoid colon of 10 UC patients and 10 patients with benign colonic polyps.Results The frequencies of mutant allele (A) and genotype (GA+AA) in FUT3 rs3745635 were higher in UC patients than in controls (P=0.016, 95%CI 1.339-1.699;P=0.038, 95%CI 1.330-1.742, respectively). Stratified analyses revealed that the frequencies of mutant allele (G) and genotype (TG+GG) of FUT3 rs28362459 were significantly lower in patients with extensive colitis than in those with distal colitis (P=0.001, 95%CI 0.567-0.786;P<0.001, 95%CI 0.503-0.742, respectively). Similar conclusions were drawn for the mutant allele (A) and genotype (GA+AA) of FUT3 rs3745635 in patients with extensive colitis compared to those with distal colitis (P=0.011, 95%CI 0.621-0.900;P=0.006, 95%CI 0.553-0.845, respectively). Although expression of Lewis b antigen in the sigmoid colon did not differ between UC patients and controls, Lewis a antigen expression was higher in the crypt epithelium of both inflammatory and non-inflammatory sigmoid colon of UC patients than in controls (P=0.028).Conclusion Polymorphisms of FUT3 and expression level of Lewis a antigen might be associated with UC.

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.