Relationship of COL9A1 and SOX9 Genes with Genetic Susceptibility of Postmenopausal Osteoporosis

  • Hongliang Liu
  • Hongmou Zhao
  • Hua Lin
  • Zhong Li
  • Hanzhong Xue
  • Yunzhi Zhang
  • Jun LuEmail author
Original Research


As one of the most common types of osteoporosis, postmenopausal osteoporosis (PMOP) is caused by both genetic and environmental factors. Previous studies have indicated that SOX9 activity is tightly regulated to ensure normal bone mineral density (BMD) in the adult skeleton, and the COL9A1 promoter region can be transactivated by SOX9. In this study, we aimed to investigate the potential association between PMOP and the COL9A1 and SOX9 genes. A total of 10,443 postmenopausal women, including 2288 patients and 3557 controls in the discovery stage and 1566 patients and 3032 controls in the validation stage, were recruited. Forty-three tag SNPs (36 in COL9A1 and 7 in SOX9) were selected for genotyping to evaluate the association of the SOX9 gene with PMOP and BMD. Association and bioinformatics analyses were performed for PMOP. BMD and serum level of SOX9 were also utilized as quantitative phenotypes in further analyses. SNP rs73354570 of SOX9 was significantly associated with PMOP in both discovery stages (OR 1.24 [1.10–1.39], P = 3.56 × 10−4, χ2 = 12.75) and combined samples (OR 1.25 [1.15–1.37], P = 5.25 × 10−7, χ2 = 25.17). Further analyses showed that the SNP was also significantly associated with BMD and serum levels of the SOX9 protein. Our results provide further supportive evidence for the association of the SOX9 gene with PMOP and of the SOX9 gene with the variation of BMD in postmenopausal Han Chinese women. This study supports a role for SOX9 in the etiology of PMOP, adding to the current understanding of the susceptibility of osteoporosis.


SOX9 COL9A1 Postmenopausal osteoporosis Common variants Genetic association Bone mineral density 


Author Contributions

Conceived and designed the experiments: Jun Lu and Hongliang Liu. Performed the experiments: Hongliang Liu and Hongmou Zhao. Analyzed the data: Hua Lin. Contributed reagents / materials / analysis tools: Zhong Li, Hanzhong Xue and Yunzhi Zhang. Wrote the paper: Hongliang Liu.

Compliance with Ethical Standards

Conflict of interest

Hongliang Liu, Hongmou Zhao, Hua Lin, Zhong Li, Hanzhong Xue, Yunzhi Zhang and Jun Lu declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This study was performed in accordance with the ethical guidelines of the Helsinki Declaration of 1975 (revised in 2008) and was approved by the Medical Ethics Committee of Honghui Hospital of Xi’an Jiaotong University. Informed consent was obtained from all subjects.

Supplementary material

223_2019_629_MOESM1_ESM.docx (575 kb)
Supplementary file1 (DOCX 575 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Hongliang Liu
    • 1
    • 2
  • Hongmou Zhao
    • 3
  • Hua Lin
    • 2
  • Zhong Li
    • 2
  • Hanzhong Xue
    • 2
  • Yunzhi Zhang
    • 4
  • Jun Lu
    • 5
    Email author
  1. 1.Department of OrthopedicThe First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
  2. 2.Department of Trauma Orthopedics, Honghui HospitalXi’an Jiaotong University Health Science CenterXi’anChina
  3. 3.Department of Foot and Ankle Surgery, Honghui HospitalXi’an Jiaotong University Health Science CenterXi’anChina
  4. 4.Department of Orthopaedic SurgeryThe Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
  5. 5.Department of Internal Medicine, Honghui HospitalXi’an Jiaotong University Health Science CenterXi’anChina

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