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

Yuka Sasaki, Kenji Ihara, Nabuo Matsuura, Hitoshi Kohno, Seiho Nagafuchi, Ryuichi Kuromaru, Koichi Kusuhara, Ryu Takeya, Timothy Hoey, Hideki Sumimoto, Toshiro Hara

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)177-184
Number of pages8
JournalHuman Genetics
Issue number3
Publication statusPublished - Aug 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


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