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Polymorphisms in genes in the RANKL/RANK/OPG pathway are associated with bone mineral density at different skeletal sites in post-menopausal women

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Abstract

Summary

Association between 22 single nucleotide polymorphisms (SNPs) in the TNFSF11, TNFRSF11A, and TNFRSF11B genes in the RANKL/RANK/OPG pathway with bone mineral density (BMD) in 881 post-menopausal women. Our results suggest that TNFSF11 and TNFRSF11A, but not TNFRSF11B, genetic polymorphisms influence BMD mainly in the femoral neck in post-menopausal Chinese women.

Introduction

The aim of this study was to assess the relationship of polymorphisms in the TNFSF11, TNFRSF11A, and TNFRSF11B genes in the RANKL/RANK/OPG pathway with bone mineral density (BMD) in a cohort of Chinese post-menopausal women.

Methods

A cross-sectional study was conducted in 881 post-menopausal women aged 50–89 years. All participants underwent lumbar spinal (LS) and femoral neck (FN) BMD evaluation by dual-energy X-ray absorptiometry. Twenty-two TNFSF11, TNFRSF11A, and TNFRSF11B SNPs were genotyped. We tested whether a single SNP or a haplotype was associated with BMD variations.

Results

Two SNPs in the TNFSF11 gene (rs2277439 and rs2324851) and one in the TNFRSF11A gene (rs7239261) were found to be significantly associated with FN BMD (p = 0.014, 0.013, and 0.047, respectively). Haplotype TGACGT of TNFSF11 rs9525641-rs2277439-rs2324851-rs2875459-rs2200287-rs9533166 was a genetic risk factor toward a lower FN BMD (beta = −0.1473; p = 0.01126). In contrary, haplotype TAGCGT of TNFSF11 rs9525641-rs2277439-rs2324851-rs2875459-rs2200287-rs9533166 was genetic protective factor for LS BMD (beta = 0.3923; p = 0.04917).

Conclusions

Our findings suggest that TNFSF11 and TNFRSF11A, but not TNFRSF11B, genetic polymorphisms influence BMD mainly in the femoral neck in post-menopausal Chinese women. This contributes to the understanding of the role of genetic variation in this pathway in determining bone health.

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Acknowledgments

This study was funded by the Key Projects of Health Department of Jiangxi Province, China (no. 20114030). We gratefully acknowledge the support of the participants in this study.

Conflicts of interest

None.

Funding

This study was funded by the Key Projects of Health Department of Jiangxi Province, China (no. 20114030).

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, The Third Hospital of Nanchang, Nanchang Key Laboratory of Diabetes, Nanchang, Jiangxi Province, 330009, China

    P. Tu, P. Duan, R.-S. Zhang, D.-B. Xu, Y. Wang, H.-P. Wu, Y.-H. Liu & L. Si

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  1. P. Tu
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  3. R.-S. Zhang
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Correspondence to P. Tu.

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Tu, P., Duan, P., Zhang, RS. et al. Polymorphisms in genes in the RANKL/RANK/OPG pathway are associated with bone mineral density at different skeletal sites in post-menopausal women. Osteoporos Int 26, 179–185 (2015). https://doi.org/10.1007/s00198-014-2854-7

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  • DOI: https://doi.org/10.1007/s00198-014-2854-7

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