title: Association of the gene encoding wingless-type mammary tumor virus integration-site family member 5B (WNT5B) with type 2 diabetes.
abstract: Recent reports have suggested that WNT signaling is an important regulator for adipogenesis or insulin secretion and might be involved in the pathogenesis of type 2 diabetes. To investigate possible roles of the WNT genes in conferring susceptibility to type 2 diabetes, we examined the association of the genes that encode members of the WNT family with type 2 diabetes in the Japanese population. First, 40 single-nucleotide polymorphism (SNP) loci within 11 WNT genes were analyzed in 188 subjects with type 2 diabetes (case-1) and 564 controls (control-1). Among them, six SNP loci exhibited a significant difference (P<.05) in the allele and/or genotype distributions between case and control subjects. These SNP loci were further analyzed in another set of case (case-2; n=733) and control (control-2; n=375) subjects to confirm their statistical significance. As a result, one SNP locus in the WNT5B gene was strongly associated with type 2 diabetes ( chi 2=15.6; P=.00008; odds ratio=1.74; 95% confidence interval 1.32-2.29). Expression of the WNT5B gene was detectable in several tissues, including adipose, pancreas, and liver. Subsequent in vitro experiments identified the fact that expression of the Wnt5b gene was increased at an early phase of adipocyte differentiation in mouse 3T3-L1 cells. Furthermore, overexpression of the Wnt5b gene in preadipocytes resulted in the promotion of adipogenesis and the enhancement of adipocytokine-gene expression. These results indicate that the WNT5B gene may contribute to conferring susceptibility to type 2 diabetes and may be involved in the pathogenesis of this disease through the regulation of adipocyte function.
authors.affiliation: Laboratory for Diabetic Nephropathy, SNP Research Center, The Institute of Physical and Chemical Research, Kanagawa, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Kanazawa
authors.forename: Syuuichi
authors.initials: S
authors.lastname: Tsukada
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sekine
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Babazono
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuda
authors.forename: Kohei
authors.initials: K
authors.lastname: Kaku
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Kikkawa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Shiro
authors.initials: S
authors.lastname: Maeda
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005786:Gene Expression Regulation; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008099:Liver / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D010179:Pancreas / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D051153:Wnt Proteins
chemical_list: D017931:DNA Primers; D011518:Proto-Oncogene Proteins; C435831:WNT5B protein, human; D051153:Wnt Proteins