A functional promoter polymorphism-607G > C of WNT10B is associated with abdominal fat in Korean female subjects

Abstract

WNT10B has been implicated as a potential regulator of adipogenesis in cellular and animal models of obesity. In this study, we attempted to characterize the associations between common genetic polymorphisms of WNT10B and fat accumulation in a sample of 1029 Korean female subjects. Direct sequencing of genomic DNAs of 45 subjects identified six common single-nucleotide polymorphisms (SNPs) of WNT10B, which were in almost complete linkage disequilibrium. Among the six SNPs, -607G>C (rs833840) showed differential nuclear factor binding in an electrophoretic mobility shift assay and differential promoter activity in a reporter assay, implicating it as a functional regulatory SNP. When body compositions of the subjects determined using bio-impedance analysis were compared according to their -607G>C genotype, only body fat mass showed a significant association. Body masses of protein, mineral and water showed no association. For more accurate evaluation of the effects of -607G>C genotype on body fat, cross-sectional fat areas of the subjects measured by abdominal computed tomography were compared. Genotype of -607G>C was significantly associated with abdominal total fat and abdominal subcutaneous fat areas (P=.009 and P=.007 in recessive model, respectively). Of the 1029 subjects, 576 were treated with a 1 month very low calorie diet and changes of body weight and composition were compared with -607G>C genotype. No significant associations were evident. This study is the first report of the association of common genetic polymorphism of WNT10B with human fat accumulation. (C) 2011 Elsevier Inc. All rights reserved.