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

Shiro Maeda¹, Shuichi Tsukada², Akio Kanazawa², Akihiro Sekine³, Tatsuhiko Tsunoda⁴, Daisuke Koya⁵, Hiroshi Maegawa⁵, Atsunori Kashiwagi⁵, Tetsuya Babazono⁶, Masafumi Matsuda⁷, Yasushi Tanaka⁸, Tomoaki Fujioka⁹, Hiroshi Hirose¹⁰, Takashi Eguchi¹⁰, Yoichi Ohno¹⁰, Christopher J Groves^{11

12}, Andrew T Hattersley¹³, Graham A Hitman¹⁴, Mark Walker¹⁵, Kohei Kaku⁷, Yasuhiko Iwamoto⁶, Ryuzo Kawamori⁸, Ryuichi Kikkawa⁵, 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. 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

Comparative Study

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

Shiro Maeda et al. J Hum Genet. 2005.

. 2005;50(6):283-292.

doi: 10.1007/s10038-005-0253-9. Epub 2005 Jun 7.

Authors

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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References

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

Affiliations

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

Authors

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Abstract

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