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 2
(
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:
2=10.9,
P=0.0009; odds ratio=1.57, 95% CI 1.20–2.06, intron 1+774 (G/T);
2=11.6,
P=0.0006; odds ratio=1.60, 95% CI 1.22–2.09, intron 1+2093 (A/C);
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.
Keywords Type 2 diabetes - Variable number of tandem repeats (VNTR) - Single nucleotide polymorphism (SNP) - Adipocytes - Association study
Accession numbers and URLs for data in this article are as follows: Genbank, http://www.ncbi.nlm.nih.gov/Genbank/ [for the TFAP2B gene (accession number NT_007592)]. For SNPs and primers, the IMS-JST Japanese SNP database (http://snp.ims.u-tokyo.ac.jp/). Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/OMIM [for type 2 diabetes (MIM 125853), TFAP2B (MIM 601601), MODY (MIM 606391), Char syndrome (MIM 169100)].