1.Association of ulcerative colitis with fork head/winged helix transcription factor-3 gene polymorphisms in Chinese patients
Daguan ZHANG ; Xuanping XIA ; Hao WU ; Xiuqing LIN ; Lijia JIANG ; Ran DING ; Yi JIANG
Chinese Journal of Internal Medicine 2017;56(3):188-193
Objective To investigate the association of ulcerative colitis (UC) with fork head/ winged helix transcription factor-3 (Foxp3) polymorphisms in Han population in Zhejiang province,China.Methods A total of 381 UC patients and 490 healthy controls were enrolled in this study.The four single nucleotide polymorphisms (SNPs) of Foxp3 (rs3761547,rs2232365,rs2294021,rs3761548) were examined by SNaPshot.The analyses of linkage disequilibrium (LD) and haplotype were also performed in all study subjects.Results When male and female UC patients were compared with their corresponding controls respectively,the alleles and genotypes of the four SNPs were not statistically different (all P >0.05).According to severity and location of the disease,the UC patients were divided into different subgroups.The alleles (C,G,A) of (rs2232365,rs2294021,rs3761548) were more frequent in male patients with severe UC than in the male controls (69.6% vs 34.3%,P =0.001;69.6% vs 34.3%,P =0.001;39.1% vs 14.4%,P =0.002,respectively).As compared with the female controls,the alleles (C,G,A) and genotypes (TC + CC,AG + GG,CA + AA) of (rs2232365,rs2294021,rs3761548) were significantly increased in the female patients with severe UC (51.9% vs 38.0%,63.5% vs 39.2%,53.8% vs21.4%,80.8% vs57.7%,84.6% vs58.4%,76.9% vs34.7%,all P<0.05).The four SNPs above were shown to be in a strong LD both in male and in female subjects.When male and female UC patients were compared with their corresponding controls respectively,nevertheless,each haplotype frequency was not statistically different (all P > 0.05).Conclusions Foxp3 (rs2232365,rs2294021,rs3761548) variations might engender the increased risk of severe UC in Chinese Han patients.
2.Analysis of single nucleotide polymorphisms and haplotypes of FCGR2A gene among patients with ulcerative colitis.
Daguan ZHANG ; Xiaoyan MIN ; Jianzhang WANG ; Yi JIANG
Chinese Journal of Medical Genetics 2016;33(6):811-815
OBJECTIVETo assess the association of several single nucleotide polymorphisms and haplotypes of the FCGR2A gene with ulcerative colitis (UC) among Chinese patients.
METHODSFor 198 UC patients and 356 healthy controls, the alleles and genotypes of the FCGR2A gene (rs1801274, rs10800309 and rs6696854) were detected with a multiplex SNaPshot technique. All subjects were also subjected to linkage disequilibrium and haplotype analyses.
RESULTSThe mutant homozygote (CC) of the FCGR2A gene rs1801274 polymorphism was less frequent among UC patients compared with the controls (5.56% vs. 11.80%, P=0.017, OR=0.440, 95%CI: 0.221-0.875). However, the allelic and genotypic distributions of other two SNPs did not differ significantly between the two groups (all P>0.05). Furthermore, no association of the three SNPs (rs1801274, rs10800309 and rs6696854) of the FCGR2A gene with the severity and location of the UC was found (all P>0.05). The three SNPs were shown to be in a strong linkage [rs1801274-rs10800309 (D'=0.863, r=0.634); rs1801274-rs6696854 (D'=0.753, r=0.546); rs10800309-rs6696854(D'=0.990, r=0.802)]. Moreover, the frequency of T-A-T haplotype was higher among the UC patients compared with the controls (67.40% vs. 60.93%, P=0.032, OR=1.326, 95%CI: 1.024-1.717).
CONCLUSIONOur findings suggested that the mutant homozygote (CC) of the FCGR2A gene (rs1801274) may have a protective role among Chinese patients with UC. Moreover, the T-A-T haplotype formed by rs1801274, rs10800309 and rs6696854 may confer a higher risk for UC.
Adult ; Asian Continental Ancestry Group ; genetics ; Colitis, Ulcerative ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Haplotypes ; genetics ; Humans ; Polymorphism, Single Nucleotide ; genetics ; Receptors, IgG ; genetics
3.Fabrication and Evaluation of Porous Keratin/chitosan (KCS) Scaffolds for Effectively Accelerating Wound Healing.
Hong Bo TAN ; Fu You WANG ; Wei DING ; Ying ZHANG ; Jing DING ; Di Xin CAI ; Kai Fu YU ; Jun YANG ; Liu YANG ; Yong Qing XU
Biomedical and Environmental Sciences 2015;28(3):178-189
OBJECTIVETo develop a dressing with desired antibacterial activity, good water maintaining ability and mechanical properties for wound healing and skin regeneration.
METHODSThe chitosan with different concentrations were added in keratin solution to form porous keratin/chitosan (KCS) scaffolds. The morphological characteristics, chemical composition, wettability, porosity, swelling ratio and degradation of the scaffolds were evaluated. The antibacterial activity was tested by using S. aureus and E. coli suspension for 2 h. And L929 fibroblast cells culture was used to evaluate the cytotoxicity of the KCS scaffolds.
RESULTSThe adding of chitosan could increase the hydrophobicity, decrease porosity, swelling ratio and degradation rate of the KCS porous scaffolds. Mechanical properties of KCS scaffolds could be enhanced and well adjusted by chitosan. KCS scaffolds could obviously decrease bacteria number. The proliferation of fibroblast cells in porous KCS patch increased firstly and then decreased with the increase of chitosan concentration. It was appropriate to add 400 μg/mL chitosan to form porous KCS scaffold for achieving best cell attachment and proliferation compared with other samples.
CONCLUSIONThe porous KCS scaffold may be used as implanted scaffold materials for promoting wound healing and skin regeneration.
Anti-Bacterial Agents ; administration & dosage ; Bandages ; Cell Line ; Cell Proliferation ; Chitosan ; Fibroblasts ; cytology ; Humans ; Keratins ; Microscopy, Electron, Scanning ; Porosity ; Spectroscopy, Fourier Transform Infrared ; Wound Healing
4.Relationship between forkhead/winged helix transcription factor 3 gene polymorphisms and susceptibility and phenotype of Crohn's disease
Daguan ZHANG ; Lebin KE ; Shuguang CAO ; Shenglong XIA ; Guangrong LU ; Xiuqing LIN ; Lijia JIANG ; Ran DING ; Yi JIANG
Chinese Journal of Digestion 2018;38(1):7-13
Objective To investigate the relationship between forkhead/winged helix transcription factor (Foxp) 3 gene polymorphisms and susceptibility and phenotype of Crohn's disease (CD) in Han nationality in Zhejiang province.Methods From January 2007 to December 2015,268 diagnosed CD patients and 490 healthy controls were enrolled.The four single nucleotide polymorphism (SNP) of Foxp3 rs3761547,rs2232365,rs2294021 and rs3761548 were examined by a SNaPshot technique,and their relation with the efficacy of infliximab was evaluated.The linkage disequilibrium (LD) and haplotype were also analyzed.Unconditional Logistic regression analysis was performed for statistical analysis.Results There was no significant difference in the four mutant alleles and genotype frequencies between 31 patients with effective infliximab treatment and 19 patients with ineffective treatment (all P>0.05).The results of LD analysis indicated that the above four SNP were in a tight linkage.The frequency of haplotype GCGC of male CD group was 29.20% (40/137),which was higher than that of male healthy control group (19.37%,43/222),and the difference was statistically significant (odd ratio (OR)=1.717,95% confidence interval (CI) 1.045 to 2.820,P=0.032).The frequency of haplotype ACGA of female CD group was 13.36% (35/262),which was lower than that of female healthy control group (19.03%,102/536),and the difference was statistically significant (OR=0.656,95%CI 0.433 to 0.995,P=0.046).The frequency of haplotype ATAC of male colon (L2) type was 25.93% (7/27),which was lower than that of ileocecal colon (L3) type (75.38%,49/65),and the difference was statistically significant (OR=0.114,95%CI 0.041 to 0.320,P<0.01).The frequency of haplotype GCGC of male L2 type was 51.85% (14/27),which was higher than that of L3 type (9.23%,6/65),and the difference was statistically significant (OR=10.590,95%CI 3.423 to 32.758,P<0.01).The frequency of haplotype ATAC of male stenotic (B2) type was 73.21% (41/56),which was higher than that of nonstenotic and nonpenetrated (B1) type (47.30%,35/74),and the difference was statistically significant (OR=0.328,95%CI 0.156 to 0.693,P=0.003).The frequency of haplotype GCGC of male B2 type was 17.86% (10/56) which was lower than that of nonstenotic and nonpenetrated (B1) type (39.19%,29/74),and the difference was statistically significant (OR=2.946,95%CI 1.295 to 6.784,P=0.009).The frequency of haplotype ACGA of male penetrated (B3) type was 71.43% (5/7),which was higher than that of nonstenotic and nonpenetrated (B1) type (12.16%,9/74),and the difference was statistically significant (OR =0.055,95% CI 0.009 to 0.329,P < 0.01).Conclusion Foxp3 (rs3761547,rs2232365,rs2294021,rs3761548) gene polymorphisms are associated with the susceptibility and phenotype of CD in Chinese Han patients,but not related with the efficacy of infliximab.
5.Associations of Crohn's disease with DR4 and DR5 gene polymorphisms.
Xinxin LIN ; Lingxiang JIN ; Chenwei PAN ; Shuzi ZHENG ; Daguan ZHANG ; Xiuqing LIN ; Ran DING ; Lijia JIANG ; Yi JIANG
Chinese Journal of Medical Genetics 2015;32(5):715-722
OBJECTIVETo assess the associations of death receptor DR4 and DR5 gene polymorphisms with Crohn's disease (CD).
METHODSA total of 295 CD patients and 490 healthy controls were recruited. Three single nucleotide polymorphisms (SNPs) of the DR4 (rs13278062, rs20575) and DR5 (rs1047266) genes were determined with a SNaPshot method. Unconditional logistic regression analysis was carried out for determining the allelic and genotypic differences of the three SNPs between CD patients and the controls, as well as the influence of the DR4 and DR5 gene polymorphisms on the clinical features of CD patients. Linkage disequilibrium and haplotype analysis were calculated by haplotype 4.2 and R language software. A gene-gene interaction model was established to analyze whether the three SNPs can exert a synergistic effect on the susceptibility to CD.
RESULTSThe mutant allele (T) and genotype (GT+TT) of DR4 (rs13278062) were increased among CD patients compared to the controls (37.12% vs. 32.04%, P = 0.040, 95%CI: 1.010-1.550; 62.71% vs. 54.90%, P = 0.032, 95%CI: 1.028-1.855, respectively). However, the allelic and genotypic frequencies of DR4 (rs20575) and DR5 (rs1047266) did not differ between the two groups (all P > 0.05). Based on the Montreal Classification Standards, the CD patients were stratified by locations and behaviors of the disease. After multiple comparison correction (P < 0.0125), compared to ileocolonic CD patients respectively, the mutant allele (T) and genotype (GT+TT) of the rs13278062 polymorphism were significantly increased in colonic CD patients (41.04% vs. 25.64%, P = 0.002, 95%CI: 0.315-0.778; 66.04% vs. 41.03%, P = 0.001, 95%CI: 0.196-0.655, respectively) and terminal ileum CD patients (41.44% vs. 25.64%, P = 0.002, 95%CI: 0.311-0.762; 74.77% vs. 41.03%, P < 0.001, 95%CI: 0.126-0.437, respectively). In comparison to penetrating CD patients, the mutant allele (T) and genotype (GT+TT) of DR4 (rs13278062) were significantly decreased in stricturing CD patients (32.29% vs. 48.91%, P = 0.007, 95%CI: 0.300-0.828; 57.29% vs. 86.96%, P = 0.001, 95%CI: 0.078-0.520, respectively). A similar conclusion was drawn for the mutant genotype (GT+TT) of DR4 (rs13278062) in non-stricturing, non-penetrating CD patients (58.82% vs. 86.96%, P = 0.001, 95%CI: 0.086-0.536). Haplotype analysis indicated that the CT haplotype formed by rs20575 and rs13278062 was increased in CD patients compared to the controls (37.1% vs. 31.8%, P = 0.029, OR=1.279, 95%CI: 1.022-1.600). The outcome of a gene-gene interaction model indicated that the mutant genotype (GT+TT) of DR4 (rs13278062) and mutant genotype (CT+TT) of DR5 (rs1047266) may play a negatively synergistic role in CD patients (B = - 0.483, OR = 0.617, P = 0.030).
CONCLUSIONThe rs13278062 polymorphism of the DR4 gene not only can confer an increased risk for CD, but may also influence the location of the lesions and the disease behaviors. The CT haplotype formed by rs20575 and rs13278062 may be an independent risk factor for CD. Furthermore, the mutant genotype (GT+TT) of DR4 (rs13278062) and mutant genotype (CT+TT) of DR5 (rs1047266) may exert a negative synergistic effect on CD.
Adult ; Crohn Disease ; genetics ; Epistasis, Genetic ; Female ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; genetics