Machida H, Tsukamoto K, Wen CY, Narumi Y, Shikuwa S, Isomoto H, Takeshima F, Mizuta Y, Niikawa N, Murata I, Kohno S. Association of polymorphic alleles of CTLA4 with inflammatory bowel disease in the Japanese. World J Gastroenterol 2005; 11(27): 4188-4193 [PMID: 16015687 DOI: 10.3748/wjg.v11.i27.4188]
Corresponding Author of This Article
Kazuhiro Tsukamoto, MD, PhD, Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. ktsuka@net.nagasaki-u.ac.jp
Article-Type of This Article
Clinical Research
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Haruhisa Machida, Hajime Isomoto, Yohei Mizuta, Fuminao Takeshima, Shigeru Kohno, Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
Kazuhiro Tsukamoto, Yukiko Narumi, Ikuo Murata, Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan
Chun-Yang Wen, Department of Molecular Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
Saburou Shikuwa, Department of Gastroenterology, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, Omura 856-8562, Japan
Norio Niikawa, Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
Author contributions: All authors contributed equally to the work.
Correspondence to: Kazuhiro Tsukamoto, MD, PhD, Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. ktsuka@net.nagasaki-u.ac.jp
Telephone: +81-95-819-2448 Fax: +81-95-819-2895
Received: November 4, 2004 Revised: November 20, 2004 Accepted: November 23, 2004 Published online: July 21, 2005
Abstract
AIM: 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 χ2 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.
