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Association between SNPs and haplotypes in the METTL21C gene and peak bone mineral density and body composition in Chinese male nuclear families

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Abstract

The methyltransferase-like 21C gene (METTL21C), which is mainly expressed in muscle, can promote the differentiation of myoblasts to myotubes and reduce glucocorticoid-induced apoptosis of osteocytes. The purpose of this study was to explore the association between single nucleotide polymorphisms of METTL21C and peak bone mineral density (BMD), body mass index, total fat mass (TFM), and total lean mass (TLM) in Chinese young men. Fifteen tagging single nucleotide polymorphisms were genotyped, and haplotype blocks were derived in 400 Chinese male nuclear families. The peak BMD of the lumbar and hip, TFM, and TLM were measured by dual-energy X-ray absorptiometry. The association analyses were performed by a quantitative transmission disequilibrium test. Both TLM and TFM had a significant positive effect on peak BMD, but the positive regulation of TLM was stronger than that of TFM. After 1000 permutations, significant within-family associations were found between rs9585961 and lumbar spine BMD and femoral neck BMD, rs9518810 and femoral neck BMD, and rs599976 and body mass index, TFM, and percentage fat mass (all P < 0.05). The association analyses with haplotypes showed that haplotype AG in block 1 was significantly associated with TFM (P = 0.031) and haplotype CAG in block 2 was significantly associated with lumbar spine BMD (P = 0.020). Our study, for the first time, demonstrates that the polymorphisms and haplotypes of METTL21C contribute to the peak BMD and TFM in Chinese males, which suggests that as a quantitative trait locus with potential pleiotropy it may have an influence on osteoporosis and obesity.

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Acknowledgments

This study was supported by the National Basic Research Program of China (2014CB942903), the National Natural Science Foundation of China (no. 81170803 and no. 81370978), the Frontier Technology Joint Research Program of the Shanghai Municipal Hospitals (SHDC12013115), the Science and Technology Commission of Shanghai Municipality (14JC1405000), the Shanghai Leading Talent Award (051), and the Science and Technology Commission of Chongqing Municipality (CSTC2013jcyjC00009). We thank all participants for their cooperation as well as Genesky Biotechnologies.

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Authors and Affiliations

  1. Division of Osteoporosis and Bone Disease, Metabolic Bone Disease and Genetic Research Unit, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Six People’s Hospital, Shanghai, 200233, China

    Fei Zhao, Li-hong Gao, Shan-shan Li, Zhan-ying Wei, Wen-zhen Fu, Jin-wei He, Yu-juan Liu, Yun-qiu Hu & Zhen-lin Zhang

  2. Department of Endocrinology, Shanxi Medical University Affiliated First Hospital, Taiyuan, 030001, China

    Fei Zhao & Jing Dong

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  1. Fei Zhao
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Correspondence to Zhen-lin Zhang.

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Zhao, F., Gao, Lh., Li, Ss. et al. Association between SNPs and haplotypes in the METTL21C gene and peak bone mineral density and body composition in Chinese male nuclear families. J Bone Miner Metab 35, 437–447 (2017). https://doi.org/10.1007/s00774-016-0774-7

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  • DOI: https://doi.org/10.1007/s00774-016-0774-7

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