title: Associations of IGFBP3 Gene Polymorphism and Gene Expression with the Risk of Osteonecrosis of the Femoral Head in a Han Population in Northern China.
abstract: The critical roles of IGFBP3 in regulating the osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells strongly indicate its potential effects on the pathogenesis of osteonecrosis of the femoral head (ONFH). In this study, we investigated the association of IGFBP3 gene polymorphism and its protein expression with the development of ONFH to further explore its molecular pathogenesis. Ligase detection reactions and enzyme-linked immunosorbent assay were used to detect the polymorphisms of rs2453839[C/T] and rs3110697[A/G] and the serum protein expression of IGFBP3 gene in 182 cases and 179 controls, respectively. The serum lipids level was also measured by automatic biochemistry analyzer. The results revealed that the recessive model of rs3110697 and the dominant model of rs2453839 were significantly associated with the increased risk of ONFH (p = 0.048, p = 0.047, respectively). The genotypes of rs2453839 were also significantly related to the clinical stages of ONFH (p = 0.017). More importantly, the serum protein expression of IGFBP3 and insulin-like growth factor 1 (IGF1) in the ONFH group were statistically increased compared with the control group (p = 0.044, p = 0.007). The serum triglyceride and low-density lipoprotein cholesterol level in the ONFH group were significantly higher than the control group (p = 0.01, p = 0.005, respectively), but the serum high-density lipoprotein cholesterol level of the ONFH group was dramatically lower than the control group (p = 0.0001). Our results showed that both the gene polymorphisms of IGFBP3 and the abnormal protein expression of serum IGFBP3 and IGF1 closely associated with the development of ONFH.
authors.affiliation: 1 Department of Orthopedics, Second Clinical College of Jilin University , Changchun, People's Republic of China .|2 The Engineering Research Center of Molecular Diagnosis and Cell Treatment for Metabolic Bone Diseases of Jilin Province , Changchun, People's Republic of China .
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.affiliation: 1 Department of Orthopedics, Second Clinical College of Jilin University , Changchun, People's Republic of China .|2 The Engineering Research Center of Molecular Diagnosis and Cell Treatment for Metabolic Bone Diseases of Jilin Province , Changchun, People's Republic of China .|3 Research Center of Second Clinical College of Jilin University , Changchun, People's Republic of China .
authors.forename: Zhenwu
authors.initials: Z
authors.lastname: Du
authors.affiliation: 2 The Engineering Research Center of Molecular Diagnosis and Cell Treatment for Metabolic Bone Diseases of Jilin Province , Changchun, People's Republic of China .|3 Research Center of Second Clinical College of Jilin University , Changchun, People's Republic of China .
authors.forename: Qiwei
authors.initials: Q
authors.lastname: Yang
authors.affiliation: 1 Department of Orthopedics, Second Clinical College of Jilin University , Changchun, People's Republic of China .|2 The Engineering Research Center of Molecular Diagnosis and Cell Treatment for Metabolic Bone Diseases of Jilin Province , Changchun, People's Republic of China .
authors.forename: Ming
authors.initials: M
authors.lastname: Ren
authors.affiliation: 2 The Engineering Research Center of Molecular Diagnosis and Cell Treatment for Metabolic Bone Diseases of Jilin Province , Changchun, People's Republic of China .|3 Research Center of Second Clinical College of Jilin University , Changchun, People's Republic of China .
authors.forename: Yujie
authors.initials: Y
authors.lastname: Sui
authors.affiliation: 2 The Engineering Research Center of Molecular Diagnosis and Cell Treatment for Metabolic Bone Diseases of Jilin Province , Changchun, People's Republic of China .|3 Research Center of Second Clinical College of Jilin University , Changchun, People's Republic of China .
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Wang
authors.affiliation: 1 Department of Orthopedics, Second Clinical College of Jilin University , Changchun, People's Republic of China .|2 The Engineering Research Center of Molecular Diagnosis and Cell Treatment for Metabolic Bone Diseases of Jilin Province , Changchun, People's Republic of China .
authors.forename: Ao
authors.initials: A
authors.lastname: Wang
authors.affiliation: 2 The Engineering Research Center of Molecular Diagnosis and Cell Treatment for Metabolic Bone Diseases of Jilin Province , Changchun, People's Republic of China .|3 Research Center of Second Clinical College of Jilin University , Changchun, People's Republic of China .
authors.forename: Haiyue
authors.initials: H
authors.lastname: Zhao
authors.affiliation: 1 Department of Orthopedics, Second Clinical College of Jilin University , Changchun, People's Republic of China .|3 Research Center of Second Clinical College of Jilin University , Changchun, People's Republic of China .
authors.forename: Jincheng
authors.initials: J
authors.lastname: Wang
authors.affiliation: 1 Department of Orthopedics, Second Clinical College of Jilin University , Changchun, People's Republic of China .|2 The Engineering Research Center of Molecular Diagnosis and Cell Treatment for Metabolic Bone Diseases of Jilin Province , Changchun, People's Republic of China .|3 Research Center of Second Clinical College of Jilin University , Changchun, People's Republic of China .
authors.forename: Guizhen
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D016022:Case-Control Studies; D002681:China; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005270:Femur Head / Q000378:metabolism / Q000473:pathology; D005271:Femur Head Necrosis / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C583557:IGF1 protein, human; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D014280:Triglycerides; D007334:Insulin-Like Growth Factor I
keywords: IGFBP3; ONFH; clinical phenotypes; gene expression; gene polymorphism