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Positive association of genetic variants in the upstream region of NKX2-3 with Crohn’s disease in Japanese patients
  1. K Yamazaki1,
  2. A Takahashi2,
  3. M Takazoe3,
  4. M Kubo4,
  5. Y Onouchi1,
  6. A Fujino5,
  7. N Kamatani3,
  8. Y Nakamura6,7,
  9. A Hata1,8
  1. 1
    Laboratory for Gastrointestinal Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan
  2. 2
    Laboratory for Statistical Analysis, SNP Research Center, RIKEN, Tokyo, Japan
  3. 3
    Department of Medicine, Division of Gastroenterology, Social Insurance Chuo General Hospital, Tokyo, Japan
  4. 4
    Laboratory for Genotyping, SNP Research Center, RIKEN, Kanagawa, Japan
  5. 5
    Department of Surgery, Keio University School of Medicine, Tokyo, Japan
  6. 6
    Laboratory of Molecular Medicine, Institute of Medical Science, The University of Tokyo, Japan
  7. 7
    SNP Research Center, RIKEN, Kanagawa, Japan
  8. 8
    Department of Public Health, Chiba University Graduate School of Medicine, Chiba, Japan
  1. Dr K Yamazaki, Laboratory for Genotyping Development, Center for Genomic Medicine, Institute of Physical and Chemical Research (RIKEN), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; kyama{at}


Background and aims: A number of genome-wide association studies have been performed as a robust means of identifying susceptibility loci for Crohn’s disease (CD). The loci detected after the completion of the HapMap project are quite concordant among these studies, suggesting that the results are reliable. Recently, the Wellcome Trust Case Control Consortium (WTCCC) reported the primary scanning of 17 000 individuals for seven diseases, including CD, and a subsequent study has validated these susceptible genetic variants in independent UK sample sets. The purpose of this study was to study the possible association of the variants reported by the WTCCC with CD in a Japanese population.

Patients and methods: A total of 484 patients with CD and 470 healthy controls were examined. Seventeen genetic variants at eight newly identified loci, including IRGM, NKX2-3 and PTPN2, were genotyped using the TaqMan assay or the invader assay.

Results: A positive association signal presumably common to different ethnic groups for rs10883365 was detected in the upstream region of NKX2-3 (p = 0.019 under the genotypic model, p = 0.0065 under the allelic model, p = 0.019 under the recessive model, p = 0.036 under the dominant model). In addition to rs10883365, marginal associations for two single nucleotide polymorphisms (SNPs) were detected in the Japanese population; rs6887695 near IL12B and rs10761659 on 10q21. Further genotype–phenotype analysis found a significant association between rs6887695 and patients with pure ileal CD.

Conclusions: The results indicate that the three loci are possible candidates for conferring susceptibility to CD in people of different ethnicities.

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