2. Academic Validation
  3. Genetic variations in the gene encoding TFAP2B are associated with type 2 diabetes mellitus

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

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. smaeda@src.riken.jp.
  • 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.

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