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

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Abstract

Summary

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 SNPscanTM 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.

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Acknowledgments

The study was supported by the National Basic Research Program of China (2014CB942903), the National Natural Science Foundation of China (81170803 and 81370978), the Frontier Technology Joint Research Program of the Shanghai municipal hospitals (SHDC 12013115), the Shanghai Leading Talents Award (051), the Science and Technology Commission of Chongqing municipality (CSTC2013jcyjC00009), the Science, and the Technology Commission of Shanghai municipality (14JC1405000).

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Authors and Affiliations

  1. 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

    Y. Zheng, C. Wang, H. Zhang, C. Shao, L.-H. Gao, S.-S. Li, W.-J. Yu, J.-W. He, W.-Z. Fu, Y.-Q. Hu, M. Li, Y.-J. Liu & Z.-L. Zhang

  2. Department of Endocrinology, Yueqing Hospital Affiliated with Wenzhou Medical University, 318 Qing-Yuan Road, Yueqing, Zhejiang, 325600, People’s Republic of China

    Y. Zheng

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The study was approved by the Ethics Committee of the Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, and signed informed consent forms were obtained from all subjects.

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Zheng, Y., Wang, C., Zhang, H. et al. 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 27, 1805–1815 (2016). https://doi.org/10.1007/s00198-015-3457-7

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