Genetic association between WNT10B polymorphisms and obesity in a Belgian case-control population is restricted to males.

The Wnt pathway has been shown to play an important role in maintenance of stem cells and cell fate decisions in embryonic and adult stem cell populations. Activation of the Wnt pathway in mesenchymal stem cells and 3 T3-L1 cells inhibits adipogenesis and can lead to osteoblastogenesis. To evaluate the role of the Wnt pathway in adipogenesis and obesity further, we analysed the genetic association between polymorphisms in WNT10B, an activator of the Wnt pathway, and various obesity parameters in a Belgian population. Four tagSNPs that captured variation of ten SNPs (MAF>5%) in a 15.2 kb region spanning the WNT10B gene and its 3' and 5' flanking regions were genotyped. Our population consisted of 1013 obese patients (BMI≥30 kg/m(2); 468 males) and 531 lean healthy individuals (18.5 kg/m(2)≤BMI≤24.9 kg/m(2); 194 males). We found a significant association with body mass index (BMI) for three of the genotyped tagSNPs (rs4018511, rs10875902, rs833841) in the male population as analysed by logistic regression. Allelic heterogeneity testing demonstrated that these associations all represent the same significant signal. Two of the three significant SNPs were also found to be associated with BMI and weight in the male population as analysed by linear regression. In conclusion, common variation in WNT10B was shown to be associated with BMI and weight in a case-control population of Belgian males. Nonetheless, replication of this result and elucidation of the molecular actions of WNT10B remain necessary.