Population-Specific Susceptibility to Crohn's Disease and Ulcerative Colitis; Dominant and Recessive Relative Risks in the Japanese Population

Authors

  • Shigeki Nakagome,

    1. Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Chiba, Japan
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  • Yasuaki Takeyama,

    1. Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Fukuoka, Japan
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  • Shuhei Mano,

    1. Graduate School of Natural Sciences, Nagoya City University, Nagoya, Japan
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  • Shotaro Sakisaka,

    1. Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Fukuoka, Japan
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  • Toshiyuki Matsui,

    1. Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan
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  • Shoji Kawamura,

    1. Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Chiba, Japan
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  • Hiroki Oota

    Corresponding author
    1. Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Chiba, Japan
      *Corresponding author: Hiroki Oota, Ph.D., Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwanoha 5-1-5, Kashiwa, Chiba 277-8562, Japan. E-mail: hiroki_oota@k.u-tokyo.ac.jp
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*Corresponding author: Hiroki Oota, Ph.D., Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwanoha 5-1-5, Kashiwa, Chiba 277-8562, Japan. E-mail: hiroki_oota@k.u-tokyo.ac.jp

Summary

Crohn's disease (CD), a type of chronic inflammatory bowel disease (IBD), is commonly found in European and East Asian countries. The calculated heritability of CD appears to be higher than that of ulcerative colitis (UC), another type of IBD. Recent genome-wide association studies (GWAS) have identified more than thirty CD-associated genes/regions in the European population. In the East Asian population, however, a clear association between CD and an associated gene has only been detected with TNFSF15. In order to determine if CD susceptibility differs geographically, nine SNPs from seven of the European CD-associated genomic regions were selected for analysis. The genotype frequencies for these SNPs were compared among the 380 collected Japanese samples, which consisted of 212 IBD cases and 168 controls. We detected a significant association of both CD and UC with only the TNFSF15 gene. Analysis by the modified genotype relative risk test (mGRR) indicated that the risk allele of TNFSF15 is dominant for CD, but is recessive for UC. These results suggest that CD and UC susceptibility differs between the Japanese and European populations. Furthermore, it is also likely that CD and UC share a causative factor which exhibits a different dominant/recessive relative risk in the Japanese population.

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