Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium.
Endocrine. 2013 Aug;44(1):107-13. doi: 10.1007/s12020-012-9824-7. Epub 2012 Oct 27.
Wingless-type MMTV integration site family, member 10B (WNT10B) is an activator of the Wnt pathway. The Wnt pathway is known to play an important role in maintenance and differentiation of stem cells and has been implicated in the origination of obesity. To evaluate the role of genetic variation in WNT10B in obesity further, we performed a mutation analysis on Belgian obese patients and control subjects. A mutation analysis of WNT10B by means of high-resolution melting curve analysis and direct sequencing was performed on 546 obese children and adolescents (mean Z-score of 2.6 ± 0.6 and 2.5 ± 0.4 respectively), 86 morbidly obese adults (mean BMI of 48.0 ± 0.4 kg/m(2)) and 447 lean, healthy controls (mean BMI of 22.1 ± 1.7 kg/m(2)). A total of five novel non-synonymous variants were identified. R228Q was the only coding, non-synonymous variant that was exclusively found in patients, but the variant did not co-segregate with obesity in the three investigated siblings. The remaining four variants were either found both in cases and in control samples (G181D) or only in control samples (A108P, S187R and P315S). The frequency of non-synonymous variants in lean individuals (0.9 %) was higher than in obese individuals (0.3 %) and familial co-segregation of the most promising variant in patients could not be demonstrated. Therefore, we conclude that variations in WNT10B do not contribute to human monogenic obesity in our population.
无翅型 MMV 整合位点家族成员 10B（WNT10B）是 Wnt 通路的激活剂。已知 Wnt 通路在维持和分化干细胞中起着重要作用，并与肥胖的起源有关。为了进一步评估 WNT10B 基因变异在肥胖中的作用，我们对比利时肥胖患者和对照进行了突变分析。对 546 名肥胖儿童和青少年（平均 Z 分数分别为 2.6 ± 0.6 和 2.5 ± 0.4）、86 名病态肥胖成年人（平均 BMI 为 48.0 ± 0.4kg/m2）和 447 名瘦健康对照者（平均 BMI 为 22.1 ± 1.7kg/m2）进行了 WNT10B 的突变分析，采用高分辨率熔解曲线分析和直接测序。共发现 5 种新的非同义变异。R228Q 是唯一的编码非同义变异，仅在患者中发现，但该变异在三个研究的兄弟姐妹中与肥胖不共分离。其余四个变异要么在病例和对照样本中均发现（G181D），要么仅在对照样本中发现（A108P、S187R 和 P315S）。瘦个体中非同义变异的频率（0.9%）高于肥胖个体（0.3%），且在患者中未能证明最有希望的变异的家族共分离。因此，我们得出结论，WNT10B 的变异在我们的人群中不会导致人类单基因肥胖。
