No important role for genetic variation in the Chibby gene in monogenic and complex obesity
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Chibby (CBY) has been identified as a potent proadipogenic factor required for adipocyte differentiation. It has been shown that CBY inhibits the canonical Wnt pathway, and therefore promotes the development of new fat cells. Our objective therefore is to investigate the contribution of rare and common genetic variation in CBY to the development of human obesity. A mutation analysis was performed on a total of 566 obese patients and 432 lean individuals. To investigate the involvement of CBY in complex obesity, we performed a genetic association analysis of the entire CBY gene region on 1,011 obese individuals and 523 control samples. Four rare, novel variants were identified in either obese patients or lean control subjects, among which two non-synonymous variations and one frameshift mutation. In addition, four previously reported CBY variants were found. In the association analysis, logistic and linear regression showed no association between common genetic variation in CBY and obesity parameters. Several novel variations were found, but no definite role in the pathogenesis of obesity could be confirmed. Results from the association analysis suggest that common variation in CBY is not a cause for obesity in the Belgian population.
KeywordsChildhood obesity Wnt pathway Mutation analysis Association study
This study was supported by a TOP-research grant from the University of Antwerp to WVH. The study was also funded by a PhD grant of the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen) to DZ. SB holds a postdoctoral fellowship obtained from the Flemish Fund for Scientific Research (F.W.O. Vlaanderen).
Conflict of interest
The authors declare that they have no conflict of interest.
- 2.World Health Organisation (2011) Obesity and overweight_fact sheet N°311. http://www.who.int/mediacentre/factsheets/fs311/en/. Accessed 28 March 2011
- 8.Kang S, Bennett CN, Gerin I, Rapp LA, Hankenson KD, Macdougald OA (2007) Wnt signaling stimulates osteoblastogenesis of mesenchymal precursors by suppressing CCAAT/enhancer-binding protein alpha and peroxisome proliferator-activated receptor gamma. J Biol Chem 282(19):14515–14524. doi: 10.1074/jbc.M700030200 PubMedCrossRefGoogle Scholar
- 9.Kawai M, Mushiake S, Bessho K, Murakami M, Namba N, Kokubu C, Michigami T, Ozono K (2007) Wnt/Lrp/beta-catenin signaling suppresses adipogenesis by inhibiting mutual activation of PPARgamma and C/EBPalpha. Biochem Biophys Res Commun 363(2):276–282. doi: 10.1016/j.bbrc.2007.08.088 PubMedCrossRefGoogle Scholar
- 22.Love D, Li FQ, Burke MC, Cyge B, Ohmitsu M, Cabello J, Larson JE, Brody SL, Cohen JC, Takemaru K (2010) Altered lung morphogenesis, epithelial cell differentiation and mechanics in mice deficient in the Wnt/beta-catenin antagonist Chibby. PLoS One 5(10):e13600. doi: 10.1371/journal.pone.0013600 PubMedCrossRefGoogle Scholar
- 31.Sigrist CJ, Cerutti L, de Castro E, Langendijk-Genevaux PS, Bulliard V, Bairoch A, Hulo N (2010) PROSITE, a protein domain database for functional characterization and annotation. Nucleic Acids Res 38 (Database issue):D161–166. doi: 10.1093/nar/gkp885
- 32.Goldenberg O, Erez E, Nimrod G, Ben-Tal N (2009) The ConSurf-DB: pre-calculated evolutionary conservation profiles of protein structures. Nucleic Acids Res 37 (Database issue):D323–327. doi: 10.1093/nar/gkn822
- 36.Ott J (2011) Documentation to LINKAGE UTILITY programs. http://linkage.rockefeller.edu/ott/linkutil.htm. Accessed 10 Feb 2011
- 37.Gauderman W, Morrison J (2009) Gene x Environment, Gene x Gene Interaction Home page. http://hydra.usc.edu/gxe/. Accessed 10 Feb 2011