A functional promoter polymorphism -607G>C of WNT10B is associated with abdominal fat in Korean female subjects.
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.
Kim
Il Chul
IC
Department of Biology, Chonnam National University, Gwangju 500-757, Republic of Korea.
Cha
Min Ho
MH
Kim
Dong Min
DM
Lee
Haeyong
H
Moon
Jin Seok
JS
Choi
Sun Mi
SM
Kim
Kil Soo
KS
Yoon
Yoosik
Y
D050153:Abdominal Fat / Q000378:metabolism*; D000328:Adult; D000704:Analysis of Variance; D044466:Asian People / Q000235:genetics; D001823:Body Composition; D001835:Body Weight; D031204:Caloric Restriction; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016014:Linear Models; D015810:Linkage Disequilibrium; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D056910:Republic of Korea; D050507:Subcutaneous Fat, Abdominal / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics*; D055815:Young Adult
D011518:Proto-Oncogene Proteins; C491119:WNT10B protein, human; D051153:Wnt Proteins