Significant Associations of SOX9 Gene Polymorphism and Gene Expression with the Risk of Osteonecrosis of the Femoral Head in a Han Population in Northern China

Sex determining region Y-box 9 (SOX9) is a key transcription factor involved in cartilage formation during the embryonic development stage and cartilage growth and repair after birth. To explore the roles of polymorphism and expression of the SOX9 gene in the development of osteonecrosis of the femoral head (ONFH), we analyzed the polymorphism of rs12601701 [A/G] and rs1042667 [A/C] and the serum protein expression of the SOX9 gene in 182 patients with ONFH and 179 healthy control subjects. Results revealed that the A-A haplotype of SOX9 gene as well as the GG and AA genotypes of rs12601701 was significantly associated with increased ONFH risk (P = 0.038) and the risk of bilateral hip lesions of ONFH (P = 0.009), respectively. The C-A, A-A, and A-G haplotypes were also statistically associated with the decreased and increased risk of bilateral hip lesions of ONFH (P = 0.03, P = 0.048, and P = 0.013), respectively, while the A-A haplotype closely related to the clinical stages of ONFH (P = 0.041). More importantly, the serum SOX9 protein expression of the ONFH group was greatly decreased compared to control group (P = 0.0001). Our results first showed that the gene polymorphism and gene expression of SOX9 were significantly associated with the risk and clinical phenotypes of ONFH and also indicate that the SOX9 gene may play a key role in the development of ONFH.