A functional promoter polymorphism −607G>C of WNT10B is associated with abdominal fat in Korean female subjects |
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Authors: | Il Chul KimMin Ho Cha Dong Min KimHaeyong Lee Jin Seok MoonSun Mi Choi Kil Soo KimYoosik Yoon |
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Affiliation: | a Department of Biology, Chonnam National University, Gwangju 500-757, Republic of Koreab Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Koreac Department of Microbiology, Chung-Ang University College of Medicine, Seoul 156-756, Republic of Koread Kirin Oriental Hospital, Seoul 137-905, Republic of Korea |
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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. |
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Keywords: | BMI, body mass index LD, Linkage disequilibrium WHR, waist hip ratio SNP, single nucleotide polymorphism VLCD, very low calorie diet |
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