Human Genetics

, Volume 115, Issue 3, pp 177–184

Identification of a novel type 1 diabetes susceptibility gene, T-bet

  • Yuka Sasaki
  • Kenji Ihara
  • Nobuo Matsuura
  • Hitoshi Kohno
  • Seiho Nagafuchi
  • Ryuichi Kuromaru
  • Koichi Kusuhara
  • Ryu Takeya
  • Timothy Hoey
  • Hideki Sumimoto
  • Toshiro Hara
Original Investigation

DOI: 10.1007/s00439-004-1146-2

Cite this article as:
Sasaki, Y., Ihara, K., Matsuura, N. et al. Hum Genet (2004) 115: 177. doi:10.1007/s00439-004-1146-2

Abstract

The gene encoding interferon (IFN)-γ, IFNG, is known as one of the candidate susceptibility genes for type 1 diabetes. In addition, cytokines, including IFN-γ, play important roles in the pathogenesis of type 1 diabetes. Therefore, we focused on the Th1-specific T-box transcription factor gene (T-bet), which contributes to the induction of the hallmark Th1 cytokine, IFN-γ. We first screened for polymorphisms in the T-bet gene and detected two microsatellite repeat polymorphisms located in intron 1 and the 3′- flanking region, and two single nucleotide polymorphisms, including a His33Gln substitution within the coding region. By association studies, the Gln-positive phenotype and (CA)14 allele in 3′-flanking region of T-bet were found to be associated with type 1 diabetes in the Japanese population. Furthermore, Gln33 T-bet showed a significantly higher transcriptional activity of the IFNG gene via a dual luciferase reporter assay. Our study suggests the first evidence of an association between type 1 diabetes and polymorphisms in the T-bet gene, and that variation in T-bet transcriptional activity may play a role in the development of type 1 diabetes, possibly through the effect on IFN-γ production in Th1 cells.

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Yuka Sasaki
    • 1
    • 3
  • Kenji Ihara
    • 1
  • Nobuo Matsuura
    • 4
  • Hitoshi Kohno
    • 5
  • Seiho Nagafuchi
    • 2
  • Ryuichi Kuromaru
    • 1
  • Koichi Kusuhara
    • 1
  • Ryu Takeya
    • 3
  • Timothy Hoey
    • 6
  • Hideki Sumimoto
    • 3
  • Toshiro Hara
    • 1
  1. 1.Department of Pediatrics, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  2. 2.Department of Internal MedicineKyushu UniversityFukuokaJapan
  3. 3.Graduate School of Medical Sciences, and Medical Institute of BioregulationKyushu UniversityFukuokaJapan
  4. 4.Department of PediatricsKitasato University School of MedicineKanagawaJapan
  5. 5.Department of Endocrinology and MetabolismFukuoka Children’s HospitalFukuokaJapan
  6. 6.Tularik Inc.USA

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