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Association Analyses of RANKL/RANK/OPG Gene Polymorphisms with Femoral Neck Compression Strength Index Variation in Caucasians

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Abstract

Femoral neck compression strength index (fCSI), a novel phenotypic parameter that integrates bone density, bone size, and body size, has significant potential to improve hip fracture risk assessment. The genetic factors underlying variations in fCSI, however, remain largely unknown. Given the important roles of the receptor activator of the nuclear factor-κB ligand/receptor activator of the nuclear factor-κB/osteoprotegerin (RANKL/RANK/OPG) pathway in the regulation of bone remodeling, we tested the associations between RANKL/RANK/OPG polymorphisms and variations in fCSI as well as its components (femoral neck bone mineral density [fBMD], femoral neck width [FNW], and weight). This was accomplished with a sample comprising 1873 subjects from 405 Caucasian nuclear families. Of the 37 total SNPs studied in these three genes, 3 SNPs, namely, rs12585014, rs7988338, and rs2148073, of RANKL were significantly associated with fCSI (P = 0.0007, 0.0007, and 0.0005, respectively) after conservative Bonferroni correction. Moreover, the three SNPs were approximately in complete linkage disequilibrium. Haplotype-based association tests corroborated the single-SNP results since haplotype 1 of block 1 of the RANKL gene achieved an even more significant association with fCSI (P = 0.0003) than any of the individual SNPs. However, we did not detect any significant associations of these genes with fBMD, FNW, or weight. In summary, our findings suggest that the RANKL gene may play an important role in variation in fCSI, independent of fBMD and non-fBMD components.

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Acknowledgments

Investigators of this work were partially supported by grants from the National Institutes of Health (R01AR050496, R21 AG027110, R01 AG026564, P50 AR055081, and R21 AA015973). The study also benefited from grants from the National Science Foundation of China, Huo Ying Dong Education Foundation, HuNan Province, **’an Jiaotong University, and the Ministry of Education of China.

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Authors and Affiliations

  1. Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, **’an Jiaotong University, **’an, 710049, People’s Republic of China

    Shan-Shan Dong, **ao-Gang Liu, Yuan Chen, Yan Guo, Liang Wang, Jian Zhao, **ang-Hong Xu & Hong-Wen Deng

  2. Departments of Orthopedic Surgery and Basic Medical Sciences, University of Missouri––Kansas City, Kansas City, MO, 64108, USA

    Dong-Hai **ong

  3. Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, Omaha, NE, 68131, USA

    Robert R. Recker

  4. College of Life Sciences and Engineering, Bei**g Jiao Tong University, Bei**g, 100044, People’s Republic of China

    Hong-Wen Deng

  5. Departments of Orthopedic Surgery and Basic Medical Sciences, University of Missouri––Kansas City, 2411 Holmes Street, Room M3-C03, Kansas City, MO, 64108-2792, USA

    Hong-Wen Deng

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  1. Shan-Shan Dong
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Correspondence to Hong-Wen Deng.

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Dong, SS., Liu, XG., Chen, Y. et al. Association Analyses of RANKL/RANK/OPG Gene Polymorphisms with Femoral Neck Compression Strength Index Variation in Caucasians. Calcif Tissue Int 85, 104–112 (2009). https://doi.org/10.1007/s00223-009-9255-5

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