title: Polymorphisms in Wnt signaling pathway genes are associated with peak bone mineral density, lean mass, and fat mass in Chinese male nuclear families.
abstract: Our objective was to investigate the associations between polymorphisms in Wnt pathway genes and peak bone mineral density (BMD) and body composition in young Chinese men. Our study identified that WNT5B and CTNNBL1 for both BMD and body composition, and WNT4 and CTNNB1 gene polymorphisms contribute to the variation in BMD and body composition in young Chinese men, respectively.
  
  
  BACKGROUND
  Our objective was to investigate the associations between polymorphisms in WNT4, WNT5B, WNT10B, WNT16, CTNNB1, and CTNNBL1 genes and peak bone mineral density (BMD), lean mass (LM), and fat mass (FM) in young Chinese men.
  
  
  METHODS
  Using SNPscan(TM) kits, 51 single-nucleotide polymorphisms (SNPs) located in the 6 genes were genotyped in a total of 1214 subjects from 399 Chinese nuclear families. BMD, total lean mass (TLM), and total fat mass (TFM) were measured using dual energy X-ray absorptiometry (DXA). The associations between the 51 SNPs and peak BMD and body composition [including the TLM, percentage lean mass (PLM), TFM, percentage fat mass (PFM), and the body mass index (BMI)] were analyzed through quantitative transmission disequilibrium tests (QTDTs).
  
  
  RESULTS
  For peak BMD, we found significant within-family associations of rs2240506, rs7308793, and rs4765830 in the WNT5B gene and rs10917157 in the WNT4 gene with the lumbar spine BMD (all P < 0.05). We detected an association of rs11830202, rs3809269, rs1029628, and rs6489301 in the WNT5B gene and rs2293303 in the CTNNB1 gene with body composition (all P < 0.05). For the CTNNBL1 gene, six SNPs (rs6126098, rs6091103, rs238303, rs6067647, rs8126174, and rs4811144) were associated with peak BMD of the lumbar spine, femoral neck, or total hip (all P < 0.05). Furthermore, two of the six SNPs (rs8126174 and rs4811144) were associated with body composition.
  
  
  CONCLUSIONS
  This study identified WNT5B and CTNNBL1 for peak BMD and body composition in males from the Han Chinese ethnic group, and the results suggest a site-specific gene regulation. The WNT4 and CTNNB1 gene polymorphisms contribute to the variation in peak BMD and body composition, respectively.
authors.affiliation: Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Road, Shanghai, 200233, People's Republic of China.|Department of Endocrinology, Yueqing Hospital Affiliated with Wenzhou Medical University, 318 Qing-Yuan Road, Yueqing, Zhejiang, 325600, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Road, Shanghai, 200233, People's Republic of China.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Road, Shanghai, 200233, People's Republic of China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Road, Shanghai, 200233, People's Republic of China.
authors.forename: C
authors.initials: C
authors.lastname: Shao
authors.affiliation: Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Road, Shanghai, 200233, People's Republic of China.
authors.forename: L-H
authors.initials: LH
authors.lastname: Gao
authors.affiliation: Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Road, Shanghai, 200233, People's Republic of China.
authors.forename: S-S
authors.initials: SS
authors.lastname: Li
authors.affiliation: Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Road, Shanghai, 200233, People's Republic of China.
authors.forename: W-J
authors.initials: WJ
authors.lastname: Yu
authors.affiliation: Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Road, Shanghai, 200233, People's Republic of China.
authors.forename: J-W
authors.initials: JW
authors.lastname: He
authors.affiliation: Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Road, Shanghai, 200233, People's Republic of China.
authors.forename: W-Z
authors.initials: WZ
authors.lastname: Fu
authors.affiliation: Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Road, Shanghai, 200233, People's Republic of China.
authors.forename: Y-Q
authors.initials: YQ
authors.lastname: Hu
authors.affiliation: Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Road, Shanghai, 200233, People's Republic of China.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.affiliation: Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Road, Shanghai, 200233, People's Republic of China.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Liu
authors.affiliation: Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Road, Shanghai, 200233, People's Republic of China. zzl2002@medmail.com.cn.
authors.forename: Z-L
authors.initials: ZL
authors.lastname: Zhang
mesh_terms: D015502:Absorptiometry, Photon / Q000379:methods; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001823:Body Composition / Q000235:genetics* / Q000502:physiology; D015992:Body Mass Index; D015519:Bone Density / Q000235:genetics* / Q000502:physiology; D005260:Female; D005272:Femur Neck / Q000502:physiology; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008159:Lumbar Vertebrae / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D020641:Polymorphism, Single Nucleotide; D060449:Wnt Signaling Pathway / Q000235:genetics* / Q000502:physiology
keywords: Body composition; Bone mineral density; Quantitative transmission disequilibrium test (QTDT); SNPs; Wnt pathway