Immunogenetics

, Volume 55, Issue 3, pp 149–156

A functional polymorphism in the promoter/enhancer region of the FOXP3/Scurfin gene associated with type 1 diabetes

  • Wafaa M. Bassuny
  • Kenji Ihara
  • Yuka Sasaki
  • Ryuichi Kuromaru
  • Hitoshi Kohno
  • Nobuo Matsuura
  • Toshiro Hara
Original Paper

DOI: 10.1007/s00251-003-0559-8

Cite this article as:
Bassuny, W.M., Ihara, K., Sasaki, Y. et al. Immunogenetics (2003) 55: 149. doi:10.1007/s00251-003-0559-8

Abstract

FOXP3/Scurfin, a member of forkhead/winged-helix proteins, is involved in the regulation of T-cell activation, and essential for normal immune homeostasis. The FOXP3/Scurfin gene is located on chromosome Xp11.23, which includes one of the type 1 diabetes susceptible loci. Therefore, we investigated whether the human FOXP3/Scurfin gene might be a new candidate gene for type 1 diabetes. We first screened the human FOXP3/Scurfin gene for microsatellite and single nucleotide polymorphisms. Next, we performed an association study between the FOXP3/Scurfin gene and type 1 diabetes. Then, the evaluation of promoter/enhancer activity of the intron with (GT)n polymorphism was performed by dual luciferase reporter assay. We demonstrated two regions contained microsatellite polymorphisms; one was (GT)n, located on intron zero and the other (TC)n on intron 5, which were under linkage-disequilibrium. The (GT)15 allele showed a significantly higher frequency in patients with type 1 diabetes than in controls (43.1% vs 32.6%, P=0.0027). The genotype frequencies of (GT)15/(GT)15 in female patients and of (GT)15 in male patients tended to be higher than those in female (P=0.064) and male (P=0.061) controls, respectively. A significant difference in the enhancer activity between (GT)15 and (GT)16 dinucleotide repeats was detected. In conclusion, the FOXP3/Scurfin gene appears to confer a significant susceptibility to type 1 diabetes in the Japanese population.

Keywords

Type 1 diabetes FOXP3/Scurfin Polymorphism Linkage disequilibrium Dual luciferase reporter assay 

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Wafaa M. Bassuny
    • 1
  • Kenji Ihara
    • 1
  • Yuka Sasaki
    • 1
  • Ryuichi Kuromaru
    • 1
  • Hitoshi Kohno
    • 2
  • Nobuo Matsuura
    • 3
  • Toshiro Hara
    • 1
  1. 1.Department of Pediatrics, Graduate School of Medical SciencesKyushu UniversityFukuoka Japan
  2. 2.Department of Endocrinology and MetabolismFukuoka Children's HospitalFukuokaJapan
  3. 3.Department of PediatricsKitasato University School of MedicineSagamiharaJapan

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