3 polymorphism is associated with common susceptibility to IBD and that HLA-DRB1*0450 alleles increase susceptibility to CD but reduce risk for UC while HLA-DRB1*1502 alleles increase susceptibility to UC but reduce CD risk. Moreover, we found individual disease risk loci: TNFSF15 and TNFα to CD and HLA-B*5201, and NFKBIL1 to UC. The genetic risk of HLA was substantially high (odds ratios ranged from 1.54 to 2.69) while that of common susceptibility loci to IBD was modest (odds ratio ranged from 1.13 to 1.24). Conclusions Results indicate that Japanese IBD susceptibility loci identified by the meta-analysis are closely associated with the HLA regions." />
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Characteristics of Japanese inflammatory bowel disease susceptibility loci
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  • 作者：Yoshiaki Arimura (1)
    Hiroyuki Isshiki (1)
    Kei Onodera (1)
    Kanna Nagaishi (2)
    Kentaro Yamashita (1)
    Tomoko Sonoda (3)
    Takayuki Matsumoto (4)
    Atsushi Takahashi (5)
    Masakazu Takazoe (6)
    Keiko Yamazaki (7)
    Michiaki Kubo (7)
    Mineko Fujimiya (2)
    Kohzoh Imai (8)
    Yasuhisa Shinomura (1)
  • 关键词：Genetic polymorphisms ; IBD ; Japan ; Meta ; analysis ; Susceptibility genes
  • 刊名：Journal of Gastroenterology
  • 出版年：2014
  • 出版时间：August 2014
  • 年：2014
  • 卷：49
  • 期：8
  • 页码：1217-1230
  • 全文大小：2,098 KB
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  • 作者单位：Yoshiaki Arimura (1)
    Hiroyuki Isshiki (1)
    Kei Onodera (1)
    Kanna Nagaishi (2)
    Kentaro Yamashita (1)
    Tomoko Sonoda (3)
    Takayuki Matsumoto (4)
    Atsushi Takahashi (5)
    Masakazu Takazoe (6)
    Keiko Yamazaki (7)
    Michiaki Kubo (7)
    Mineko Fujimiya (2)
    Kohzoh Imai (8)
    Yasuhisa Shinomura (1)

    1. Department of Gastroenterology, Rheumatology, and Clinical Immunology, Sapporo Medical University, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan
    2. Department of Anatomy, Sapporo Medical University, Sapporo, Japan
    3. Department of Public Health, Sapporo Medical University, Sapporo, Japan
    4. Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
    5. Laboratory for Statistical Analysis, Center for Integrative Medical Science, RIKEN, Tokyo, Japan
    6. Division of Gastroenterology, Department of Medicine, Social Insurance Chuo General Hospital, Tokyo, Japan
    7. Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan
    8. Center for Antibody and Vaccine Therapy, Institute of Medical Science, University of Tokyo, Tokyo, Japan
  • ISSN：1435-5922
文摘
Background There are substantial differences in inflammatory bowel disease (IBD) genetics depending on the populations examined. We aimed to identify Japanese population-specific or true culprit susceptibility genes through a meta-analysis of past genetic studies of Japanese IBD. Methods For this study, we reviewed 2,703 articles. The review process consisted of three screening stages: we initially searched for relevant studies and then relevant single nucleotide polymorphisms (SNPs). Finally, we adjusted them for the meta-analysis. To maximize our chances of analysis, we introduced proxy SNPs during the first stage. To minimize publication bias, no significant SNPs and solitary SNPs without pairs were combined to be reconsidered during the third stage. Additionally, two SNPs were newly genotyped. Finally, we conducted a meta-analysis of 37 published studies in 50 SNPs located at 22 loci corresponding to the total number of 4,853 Crohn’s disease (CD), 5,612 ulcerative colitis (UC) patients, and 14,239 healthy controls. Results We confirmed that the NKX2-em class="a-plus-plus">3 polymorphism is associated with common susceptibility to IBD and that HLA-DRB1*0450 alleles increase susceptibility to CD but reduce risk for UC while HLA-DRB1*1502 alleles increase susceptibility to UC but reduce CD risk. Moreover, we found individual disease risk loci: TNFSF15 and TNFα to CD and HLA-B*5201, and NFKBIL1 to UC. The genetic risk of HLA was substantially high (odds ratios ranged from 1.54 to 2.69) while that of common susceptibility loci to IBD was modest (odds ratio ranged from 1.13 to 1.24). Conclusions Results indicate that Japanese IBD susceptibility loci identified by the meta-analysis are closely associated with the HLA regions.

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