Calcified Tissue International

, Volume 85, Issue 2, pp 104–112

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

  • Shan-Shan Dong
  • Xiao-Gang Liu
  • Yuan Chen
  • Yan Guo
  • Liang Wang
  • Jian Zhao
  • Dong-Hai Xiong
  • Xiang-Hong Xu
  • Robert R. Recker
  • Hong-Wen Deng
Article

DOI: 10.1007/s00223-009-9255-5

Cite this article as:
Dong, SS., Liu, XG., Chen, Y. et al. Calcif Tissue Int (2009) 85: 104. doi:10.1007/s00223-009-9255-5

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.

Keywords

Femoral neck compression strength index Femoral neck bone mineral density Femoral neck width RANKL/RANK/OPG gene Quantitative transmission disequilibrium test 

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Shan-Shan Dong
    • 1
  • Xiao-Gang Liu
    • 1
  • Yuan Chen
    • 1
  • Yan Guo
    • 1
  • Liang Wang
    • 1
  • Jian Zhao
    • 1
  • Dong-Hai Xiong
    • 2
  • Xiang-Hong Xu
    • 1
  • Robert R. Recker
    • 3
  • Hong-Wen Deng
    • 1
    • 4
    • 5
  1. 1.Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and TechnologyXi’an Jiaotong UniversityXi’anPeople’s Republic of China
  2. 2.Departments of Orthopedic Surgery and Basic Medical SciencesUniversity of Missouri––Kansas CityKansas CityUSA
  3. 3.Osteoporosis Research Center and Department of Biomedical SciencesCreighton UniversityOmahaUSA
  4. 4.College of Life Sciences and EngineeringBeijing Jiao Tong UniversityBeijingPeople’s Republic of China
  5. 5.Departments of Orthopedic Surgery and Basic Medical SciencesUniversity of Missouri––Kansas CityKansas CityUSA