Association of polymorphic alleles of CTLA4 with inflammatory bowel disease in the Japanese |
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Authors: | Machida Haruhisa Tsukamoto Kazuhiro Wen Chun-Yang Narumi Yukiko Shikuwa Saburou Isomoto Hajime Takeshima Fuminao Mizuta Yohei Niikawa Norio Murata Ikuo Kohno Shigeru |
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Affiliation: | 1. Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan 2. Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521,Japan 3. Department of Molecular Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523,Japan 4. Department of Gastroenterology, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara,Omura 856-8562, Japan 5. Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan |
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Abstract: | AM: To examine an association between the cytotoxic T-lymphocyte 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+49G in exon 1 and G+6230A in the 3' untranslated region (3'-UTR) by a PCR-restriction fragment length polymorphism method, and to an (AT)n 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 X2 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. |
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Keywords: | Ulcerative colitis CTLA4 gene Disease-susceptible gene Crohn's disease Fistula formation |
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