AIM: To examine an association between the cytotoxic Tlymphocyte antigen 4 (CTLA4) gene that plays a role in downregulation of T-cell activation and inflammatory bowel disease consisting of ulcerative colitis (UC...AIM: To examine an association between the cytotoxic Tlymphocyte antigen 4 (CTLA4) gene that plays a role in downregulation of T-cell activation and inflammatory bowel disease consisting of ulcerative colitis (UC) and Crohn's disease (CD) in the Japanese.METHODS: We studied 108 patients with UC, 79 patients with CD, and 200 sex-matched healthy controls, with respect to three single nucleotide polymorphisms (SNPs) in CTLA4, such as C-318T in the promoter region, A+49 Gin exon 1 and G+6230A in the 3' untranslated region (3'-UTR) by a PCR-restriction fragment length polymorphism method, and to an (AT), repeat polymorphism in 3'-UTR by fragment analysis with fluorescence-labeling on denaturing sequence gels. Frequency of alleles and genotypes and their distribution were compared statistically between patients and controls and among subgroups of patients, using X^2 and Fisher exact tests.RESULTS: The frequency of "A/A" genotype at the G+6230A SNP site was statistically lower in UC patients than in controls (3.7% vs 11.0%, P = 0.047, odds ratio (OR) = 0.311). Moreover, the frequency of "G/G" genotype at the A+49G SNP site was significantly higher in CD patients with fistula (48.6%) than those without it (26.2%)(P = 0.0388, OR=2.67).CONCLUSION: The results suggest that CTLA4 located at 2q33 is a determinant of UC and responsible for fistula formation in CD in the Japanese.展开更多
AIM: The goal of the current work was to analyse the prevalence of the +49A/G variant of the cytotoxic T-lymphocyte antigen 4 gene (CTLA4) in Hungarian patients with Crohn's disease (CD) and ulcerative colitis ...AIM: The goal of the current work was to analyse the prevalence of the +49A/G variant of the cytotoxic T-lymphocyte antigen 4 gene (CTLA4) in Hungarian patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: A total of 130 unrelated subjects with CD and 150 with UC, and 170 matched controls were genotyped for the single nucleotide polymorphism (SNP). The genotypes were determined by using PCR/RFLP test. RESULTS: The G allele frequency and the prevalence of the GG genotype were 38.1% and 12.3% in the CD group, 40.6% and 18.6% in the UC patients, and 37.4% and 15.9% in the control group, respectively. CONCLUSION: The results of the current study show that carriage of the +49G SNP in heterozygous or in homozygous form does not confer risk either for CD or for UC in the Hungarian population.展开更多
AIM:To evaluate the local expression of CTLA4Ig gene in small bowels and its effect on preventing acute rejection of the small bowel allografts.METHODS:Groups of Wistar rats underwent heterotopic small bowel transplan...AIM:To evaluate the local expression of CTLA4Ig gene in small bowels and its effect on preventing acute rejection of the small bowel allografts.METHODS:Groups of Wistar rats underwent heterotopic small bowel transplantation from SD rats.The recipients were randomly divided into experimental group (allografts were transfected with CTLA4Ig gene) and control group (non CTLA4Ig gene transfected).In the experimental group, the donor small bowels were perfused ex vivo with CTLA4Ig cDNA packaged with lipofectin vector via intra-superior mesenteric artery before transplantation, and the CTLA4Ig expression in the small bowel grafts post-transplantation was assessed by immunohistology. On d 3, 7 and 10 post-transplantation,the allografts in each group were harvested for the examination of histology and detection of apoptosis.RESULTS:Small bowel allografts treated with CTLA4Ig cDNA showed abundant CTLA4Ig expression after transplantation.Acute rejection of grade I on d 7 and grade Ⅱ on d 10 after transplantation was noticed in the control allografts,and a dramatically increased number of apoptotic enterocytes in parallel to the progressive rejection could be recognized.In contrast,the allografts treated with CTLA4Ig cDNA showed nonspecific histological changes and only a few apoptotic enterocytes were found after transplantation.CONCLUSION: Local CTLA4Ig gene transfection of small bowel allograft is feasible, and the local CTLA4Ig expression in the allograft can prevent acute rejection after transplantation.展开更多
文摘AIM: To examine an association between the cytotoxic Tlymphocyte antigen 4 (CTLA4) gene that plays a role in downregulation of T-cell activation and inflammatory bowel disease consisting of ulcerative colitis (UC) and Crohn's disease (CD) in the Japanese.METHODS: We studied 108 patients with UC, 79 patients with CD, and 200 sex-matched healthy controls, with respect to three single nucleotide polymorphisms (SNPs) in CTLA4, such as C-318T in the promoter region, A+49 Gin exon 1 and G+6230A in the 3' untranslated region (3'-UTR) by a PCR-restriction fragment length polymorphism method, and to an (AT), repeat polymorphism in 3'-UTR by fragment analysis with fluorescence-labeling on denaturing sequence gels. Frequency of alleles and genotypes and their distribution were compared statistically between patients and controls and among subgroups of patients, using X^2 and Fisher exact tests.RESULTS: The frequency of "A/A" genotype at the G+6230A SNP site was statistically lower in UC patients than in controls (3.7% vs 11.0%, P = 0.047, odds ratio (OR) = 0.311). Moreover, the frequency of "G/G" genotype at the A+49G SNP site was significantly higher in CD patients with fistula (48.6%) than those without it (26.2%)(P = 0.0388, OR=2.67).CONCLUSION: The results suggest that CTLA4 located at 2q33 is a determinant of UC and responsible for fistula formation in CD in the Japanese.
基金Supported by the grants of Hungarian Science Foundation (OTKA T 0495X9)Hungarian Ministry of Health (ETT 497/2006)by the National Office for Research and Technology, "Pazmany Peter" program. (RET- II 08/2005)
文摘AIM: The goal of the current work was to analyse the prevalence of the +49A/G variant of the cytotoxic T-lymphocyte antigen 4 gene (CTLA4) in Hungarian patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: A total of 130 unrelated subjects with CD and 150 with UC, and 170 matched controls were genotyped for the single nucleotide polymorphism (SNP). The genotypes were determined by using PCR/RFLP test. RESULTS: The G allele frequency and the prevalence of the GG genotype were 38.1% and 12.3% in the CD group, 40.6% and 18.6% in the UC patients, and 37.4% and 15.9% in the control group, respectively. CONCLUSION: The results of the current study show that carriage of the +49G SNP in heterozygous or in homozygous form does not confer risk either for CD or for UC in the Hungarian population.
基金Supported by the Innovative Foundation of Nanjing Medical University,N0.200106
文摘AIM:To evaluate the local expression of CTLA4Ig gene in small bowels and its effect on preventing acute rejection of the small bowel allografts.METHODS:Groups of Wistar rats underwent heterotopic small bowel transplantation from SD rats.The recipients were randomly divided into experimental group (allografts were transfected with CTLA4Ig gene) and control group (non CTLA4Ig gene transfected).In the experimental group, the donor small bowels were perfused ex vivo with CTLA4Ig cDNA packaged with lipofectin vector via intra-superior mesenteric artery before transplantation, and the CTLA4Ig expression in the small bowel grafts post-transplantation was assessed by immunohistology. On d 3, 7 and 10 post-transplantation,the allografts in each group were harvested for the examination of histology and detection of apoptosis.RESULTS:Small bowel allografts treated with CTLA4Ig cDNA showed abundant CTLA4Ig expression after transplantation.Acute rejection of grade I on d 7 and grade Ⅱ on d 10 after transplantation was noticed in the control allografts,and a dramatically increased number of apoptotic enterocytes in parallel to the progressive rejection could be recognized.In contrast,the allografts treated with CTLA4Ig cDNA showed nonspecific histological changes and only a few apoptotic enterocytes were found after transplantation.CONCLUSION: Local CTLA4Ig gene transfection of small bowel allograft is feasible, and the local CTLA4Ig expression in the allograft can prevent acute rejection after transplantation.