Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium.
Mol Biol Rep. 2013 Jul;40(7):4491-8. doi: 10.1007/s11033-013-2541-3. Epub 2013 May 5.
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.
Chibby (CBY) 已被确定为脂肪细胞分化所必需的强效促脂肪生成因子。研究表明，CBY 抑制经典 Wnt 通路，从而促进新脂肪细胞的发育。因此，我们的目标是研究 CBY 中的罕见和常见遗传变异对人类肥胖的发展的贡献。对总共 566 名肥胖患者和 432 名瘦个体进行了突变分析。为了研究 CBY 在复杂肥胖中的作用，我们对 1011 名肥胖个体和 523 名对照样本进行了整个 CBY 基因区域的遗传关联分析。在肥胖患者或瘦对照个体中发现了四个罕见的、新的变异体，其中包括两个非同义变异和一个移码突变。此外，还发现了四个先前报道的 CBY 变体。在关联分析中，逻辑回归和线性回归显示 CBY 中的常见遗传变异与肥胖参数之间没有关联。发现了一些新的变异体，但不能确定它们在肥胖发病机制中的明确作用。关联分析的结果表明，CBY 中的常见变异不是比利时人群肥胖的原因。
