Genetic variations in the gene encoding TFAP2B are associated with type 2 diabetes mellitus

  • J Hum Genet. 2005;50(6):283-292. doi: 10.1007/s10038-005-0253-9.
Shiro Maeda  1 ,  Shuichi Tsukada  2 ,  Akio Kanazawa  2 ,  Akihiro Sekine  3 ,  Tatsuhiko Tsunoda  4 ,  Daisuke Koya  5 ,  Hiroshi Maegawa  5 ,  Atsunori Kashiwagi  5 ,  Tetsuya Babazono  6 ,  Masafumi Matsuda  7 ,  Yasushi Tanaka  8 ,  Tomoaki Fujioka  9 ,  Hiroshi Hirose  10 ,  Takashi Eguchi  10 ,  Yoichi Ohno  10 ,  Christopher J Groves  11  12 ,  Andrew T Hattersley  13 ,  Graham A Hitman  14 ,  Mark Walker  15 ,  Kohei Kaku  7 ,  Yasuhiko Iwamoto  6 ,  Ryuzo Kawamori  8 ,  Ryuichi Kikkawa  5 ,  Naoyuki Kamatani  16  17 ,  Mark I McCarthy  11  12 ,  Yusuke Nakamura  17  18
Affiliations
  • 1. Laboratory for Diabetic Nephropathy, SNP Research Center, The Institute of Physical and Chemical Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan. [email protected].
  • 2. Laboratory for Diabetic Nephropathy, SNP Research Center, The Institute of Physical and Chemical Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
  • 3. Laboratory for Genotyping, SNP Research Center, The Institute of Physical and Chemical Research, Kanagawa, Japan.
  • 4. Laboratory for Medical Informatics, SNP Research Center, The Institute of Physical and Chemical Research, Kanagawa, Japan.
  • 5. Department of Medicine, Shiga University of Medical Science, Shiga, Japan.
  • 6. Diabetes Center, Tokyo Women's Medical University, Tokyo, Japan.
  • 7. Division of Endocrinology and Metabolism, Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan.
  • 8. Department of Medicine, Metabolism and Endocrinology, School of Medicine, Juntendo University, Tokyo, Japan.
  • 9. Department of Urology, Iwate Medical University School of Medicine, Iwate, Japan.
  • 10. Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
  • 11. Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK.
  • 12. Wellcome Trust Centre for Human Genetics, Oxford, UK.
  • 13. Centre for Molecular Genetics, Peninsula Medical School, Exeter, UK.
  • 14. Centre of Diabetes and Metabolic Medicine, Bart's and The London, Queen Mary's School of Medicine and Dentistry, London, UK.
  • 15. School of Clinical Medical Sciences, University of Newcastle, Newcastle, UK.
  • 16. Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
  • 17. Research Group for Personalized Medicine, SNP Research Center, The Institute of Physical and Chemical Research, Kanagawa, Japan.
  • 18. Laboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.
PMID: 15940393 DOI: 10.1007/s10038-005-0253-9
Abstract

To search a gene(s) conferring susceptibility to type 2 diabetes mellitus, we genotyped nearly 60,000 gene-based SNPs for Japanese patients and found evidence that the gene at chromosome 6p12 encoding transcription-factor-activating protein 2beta (TFAP2B) was a likely candidate in view of significant association of polymorphism in this gene with type 2 diabetes. Extensive analysis of this region identified that several variations within TFAP2B were significantly associated with type 2 diabetes [a variable number of tandem repeat locus: chi(2)=10.9, P=0.0009; odds ratio=1.57, 95% CI 1.20-2.06, intron 1+774 (G/T); chi(2)=11.6, P=0.0006; odds ratio=1.60, 95% CI 1.22-2.09, intron 1+2093 (A/C); chi(2)=12.2, P=0.0004; odds ratio=1.61, 95% CI 1.23-2.11]. The association of TFAP2B with type 2 diabetes was also observed in the UK population. These results suggest that TFAP2B might be a new candidate for conferring susceptibility to type 2 diabetes and contribute to the pathogenesis of type 2 diabetes.