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

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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.

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Acknowledgements

We are grateful to Drs. M. Saito and F. Nakatani for their technical assistance and pertinent advice. This work was supported by a Grant-in Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and a grant from Japan Study Group for Pediatric and Adolescent Diabetes.

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Authors and Affiliations

  1. Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, 812-8582, Fukuoka , Japan

    Wafaa M. Bassuny, Kenji Ihara, Yuka Sasaki, Ryuichi Kuromaru & Toshiro Hara

  2. Department of Endocrinology and Metabolism, Fukuoka Children's Hospital, Fukuoka, Japan

    Hitoshi Kohno

  3. Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan

    Nobuo Matsuura

Authors
  1. Wafaa M. Bassuny
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  2. Kenji Ihara
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  3. Yuka Sasaki
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  4. Ryuichi Kuromaru
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  5. Hitoshi Kohno
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  6. Nobuo Matsuura
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  7. Toshiro Hara
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Correspondence to Wafaa M. Bassuny.

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Bassuny, W.M., Ihara, K., Sasaki, Y. et al. A functional polymorphism in the promoter/enhancer region of the FOXP3/Scurfin gene associated with type 1 diabetes. Immunogenetics 55, 149–156 (2003). https://doi.org/10.1007/s00251-003-0559-8

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  • DOI: https://doi.org/10.1007/s00251-003-0559-8

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