Relationship of COL9A1 and SOX9 genes with genetic susceptibility of postmenopausal osteoporosis

Liu, Hongliang; Zhao, Hongmou; Lin, Hua; Li, Zhong; Xue, Hanzhong; Zhang, Yunzhi; Lu, Jun

Affiliations

¹Department of Orthopedic, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

²Department of Trauma Orthopedics, Honghui Hospital, Xi’an Jiaotong University Health Science Center, Xi’an, China

³Department of Foot and Ankle Surgery, Honghui Hospital, Xi’an Jiaotong University Health Science Center, Xi’an, China

⁴Department of Orthopaedic Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

⁵Department of Internal Medicine, Honghui Hospital, Xi’an Jiaotong University Health Science Center, Xi’an, China

Abstract and keywords

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.

Keywords: SOX9; COL9A1; Postmenopausal osteoporosis; Common variants; Genetic association; Bone mineral density

Links

DOI: 10.1007/s00223-019-00629-7

PubMed: 31732751

WoS: 000513185400004

History

Received: 2019-08-06

Accepted: 2019-10-29

Online: 2019-11-15

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