Clinical Research
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2005; 11(31): 4833-4837
Published online Aug 21, 2005. doi: 10.3748/wjg.v11.i31.4833
Crohn’s disease in Japanese is associated with a SNP-haplotype of N-acetyltransferase 2 gene
Haruhisa Machida, Kazuhiro Tsukamoto, Chun-Yang Wen, Saburou Shikuwa, Hajime Isomoto, Yohei Mizuta, Fuminao Takeshima, Kunihiko Murase, Naomichi Matsumoto, Ikuo Murata, Shigeru Kohno, Chen-Yang Wen
Haruhisa Machida, Hajime Isomoto, Yohei Mizuta, Fuminao Takeshima, Kunihiko Murase, Shigeru Kohno, Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
Kazuhiro Tsukamoto, Ikuo Murata, Department of Pharmaco-therapeutics, 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
Chen-Yang Wen, Department of Digestive Disease, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
Saburou Shikuwa, Department of Gastroenterology, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, Omura 856-8562, Japan
Naomichi Matsumoto, Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
Kazuhiro Tsukamoto, Naomichi Matsumoto, CREST, JST, Kawaguchi, 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: December 20, 2004
Revised: December 23, 2004
Accepted: December 30, 2004
Published online: August 21, 2005
Abstract

AIM: To investigate the frequency and distribution of N-acetyltransferase 2 (NAT2) and uridine 5’-diphosphate (UDP)-glucuronosyltransferase 1A7 (UGT1A7) genes in patients with ulcerative colitis (UC) and Crohn’s disease (CD).

METHODS: Frequencies and distributions of NAT2 and UGT1A7 SNPs as well as their haplotypes were investigated in 95 patients with UC, 60 patients with CD, and 200 gender-matched, unrelated, healthy, control volunteers by PCR-restriction fragment length polymorphism (RFLP), PCR-denaturing high-performance liquid chromatography (DHPLC), and direct DNA sequencing.

RESULTS: Multiple logistic regression analysis revealed that the frequency of haplotype, NAT2*7B, significantly increased in CD patients, compared to that in controls (P = 0.0130, OR = 2.802, 95%CI = 1.243-6.316). However, there was no association between NAT2 haplotypes and UC, or between any UGT1A7 haplotypes and inflammatory bowel disease (IBD).

CONCLUSION: It is likely that the NAT2 gene is one of the determinants for CD in Japanese. Alternatively, a new CD determinant may exist in the 8p22 region, where NAT2 is located.

Keywords: Crohn’s disease, N-acetyltransferase 2 gene, Polymorphism, Disease-susceptible gene, Association study, Japanese population