Polymorphisms in Wnt signaling pathway genes are associated with peak bone mineral density, lean mass, and fat mass in Chinese male nuclear families

Osteoporos Int. 2016 May;27(5):1805-15. doi: 10.1007/s00198-015-3457-7. Epub 2016 Jan 5.

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.

Introduction: 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.

Keywords: Body composition; Bone mineral density; Quantitative transmission disequilibrium test (QTDT); SNPs; Wnt pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon / methods
  • Adult
  • Aged
  • Asian Continental Ancestry Group / genetics*
  • Body Composition / genetics*
  • Body Composition / physiology
  • Body Mass Index
  • Bone Density / genetics*
  • Bone Density / physiology
  • Female
  • Femur Neck / physiology
  • Genetic Association Studies
  • Genotype
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Lumbar Vertebrae / physiology
  • Male
  • Middle Aged
  • Nuclear Family
  • Polymorphism, Single Nucleotide*
  • Wnt Signaling Pathway / genetics*
  • Wnt Signaling Pathway / physiology