Genetic variations in the gene encoding TFAP2B are associated with type 2 diabetes mellitus.
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.
Maeda
Shiro
S
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.
Tsukada
Shuichi
S
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.
Kanazawa
Akio
A
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.
Sekine
Akihiro
A
Laboratory for Genotyping, SNP Research Center, The Institute of Physical and Chemical Research, Kanagawa, Japan.
Tsunoda
Tatsuhiko
T
Laboratory for Medical Informatics, SNP Research Center, The Institute of Physical and Chemical Research, Kanagawa, Japan.
Koya
Daisuke
D
Department of Medicine, Shiga University of Medical Science, Shiga, Japan.
Maegawa
Hiroshi
H
Department of Medicine, Shiga University of Medical Science, Shiga, Japan.
Kashiwagi
Atsunori
A
Department of Medicine, Shiga University of Medical Science, Shiga, Japan.
Babazono
Tetsuya
T
Diabetes Center, Tokyo Women's Medical University, Tokyo, Japan.
Matsuda
Masafumi
M
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan.
Tanaka
Yasushi
Y
Department of Medicine, Metabolism and Endocrinology, School of Medicine, Juntendo University, Tokyo, Japan.
Fujioka
Tomoaki
T
Department of Urology, Iwate Medical University School of Medicine, Iwate, Japan.
Hirose
Hiroshi
H
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Eguchi
Takashi
T
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Ohno
Yoichi
Y
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Groves
Christopher J
CJ
Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK.|Wellcome Trust Centre for Human Genetics, Oxford, UK.
Hattersley
Andrew T
AT
Centre for Molecular Genetics, Peninsula Medical School, Exeter, UK.
Hitman
Graham A
GA
Centre of Diabetes and Metabolic Medicine, Bart's and The London, Queen Mary's School of Medicine and Dentistry, London, UK.
Walker
Mark
M
School of Clinical Medical Sciences, University of Newcastle, Newcastle, UK.
Kaku
Kohei
K
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan.
Iwamoto
Yasuhiko
Y
Diabetes Center, Tokyo Women's Medical University, Tokyo, Japan.
Kawamori
Ryuzo
R
Department of Medicine, Metabolism and Endocrinology, School of Medicine, Juntendo University, Tokyo, Japan.
Kikkawa
Ryuichi
R
Department of Medicine, Shiga University of Medical Science, Shiga, Japan.
Kamatani
Naoyuki
N
Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.|Research Group for Personalized Medicine, SNP Research Center, The Institute of Physical and Chemical Research, Kanagawa, Japan.
McCarthy
Mark I
MI
Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK.|Wellcome Trust Centre for Human Genetics, Oxford, UK.
Nakamura
Yusuke
Y
Research Group for Personalized Medicine, SNP Research Center, The Institute of Physical and Chemical Research, Kanagawa, Japan.|Laboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.
D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D006113:United Kingdom
D017931:DNA Primers; D004268:DNA-Binding Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors