Association of SREBP2 gene polymorphisms with the risk of osteonecrosis of the femoral head relates to gene expression and lipid metabolism disorders

Song,Yang; Du,Zhenwu; Chen,Bingpeng; Ren,Ming; Yang,Qiwei; Sui,Yujie; Wang,Qingyu; Wang,Ao; Zhao,Haiyue; Qin,Yanguo; Zhang,Guizhen

doi:10.3892/mmr.2017.7473

Association of SREBP2 gene polymorphisms with the risk of osteonecrosis of the femoral head relates to gene expression and lipid metabolism disorders

Authors:
- Yang Song
- Zhenwu Du
- Bingpeng Chen
- Ming Ren
- Qiwei Yang
- Yujie Sui
- Qingyu Wang
- Ao Wang
- Haiyue Zhao
- Yanguo Qin
- Guizhen Zhang
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Affiliations: Department of Orthopedics of the Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China, The Engineering Research Center of Molecular Diagnosis and Cellular Treatment for Metabolic Bone Diseases of Jilin Province, Changchun, Jilin 130041, P.R. China
Published online on: September 12, 2017 https://doi.org/10.3892/mmr.2017.7473
Pages: 7145-7153

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Abstract

Although lipid metabolism disorders have been recognized as a primary factor of osteonecrosis of the femoral head (ONFH), the molecular pathogenesis remains unclear. Sterol regulatory element‑binding protein 2 (SREBP2) specifically regulates cholesterol and fatty acid metabolism to maintain lipid homeostasis. To explore the roles of the SREBP2 gene in the development of ONFH, the authors analyzed the gene polymorphism and gene expression of three tag single nucleotide polymorphisms of the SREBP2 gene, the serum lipids levels, and their associations with ONFH development in 182 ONFH patients and 179 healthy controls. The results demonstrated that the stage IV proportions of ONFH patients carrying the rs2267439CT or CC genotype were significantly higher and lower than the stage III proportions of ONFH patients (P=0.039), respectively. The serum triglyceride, low‑density lipoprotein (LDL)‑c levels, and LDL‑C/high‑density lipoprotein (HDL)‑C ratio in the ONFH group were significantly increased compared to those in the control group (P=0.01, P=0.005, P=0.0001) while the HDL‑C level of ONFH group was remarkably lower than that of the control group (P=0.0001). Association analysis further revealed that the LDL‑c levels of the rs226744 GG and AG genotype carriers were statistically higher than that of the AA genotype carriers (P=0.039, P=0.05). These results demonstrated that the gene polymorphism of SREBP2 not only significantly associated with the clinical phenotypes of ONFH but also closely related to lipid metabolism disorder. The results indicated that SREBP2 gene polymorphism and function may play key roles in the development of ONFH.

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