Association of Genes Variants in RANKL/RANK/OPG Signaling Pathway with the Development of Osteonecrosis of the Femoral Head in Chinese Population

Yang Song; Zhen-Wu Du; Qi-Wei Yang; Ming Ren; Qing-Yu Wang; Ao Wang; Gao-Yang Chen; Hai-Yue Zhao; Tao Yu; Gui-Zhen Zhang

doi:10.7150/ijms.19124

Association of Genes Variants in RANKL/RANK/OPG Signaling Pathway with the Development of Osteonecrosis of the Femoral Head in Chinese Population

Int J Med Sci. 2017 Jun 23;14(7):690-697. doi: 10.7150/ijms.19124. eCollection 2017.

Authors

Yang Song^{1

2}, Zhen-Wu Du^{1

3

2}, Qi-Wei Yang^{3

2}, Ming Ren^{1

3}, Qing-Yu Wang^{3

2}, Ao Wang^{1

2}, Gao-Yang Chen^{3

2}, Hai-Yue Zhao^{3

2}, Tao Yu^{1

3}, Gui-Zhen Zhang^{1

3

2}

Affiliations

¹ Department of Orthopedics of Second Clinical College, Jilin University, Changchun, 130041, China.
² The Engineering Research Center of Molecular Diagnosis and Cell Treatment for Metabolic Bone Diseases of Jilin Province, Changchun, 130041, China.
³ Research Center of Second Clinical College, Jilin University, Changchun, 130041, China.

Abstract

The RANKL/RANK/OPG pathway plays an important role in regulating bone remodeling and bone turnover. However, the association of the genes variants with the risk of ONFH has rarely been reported. Here, we analyzed the correlation of the 10 SNPs polymorphisms of RANKL, RANK, OPG, TRAF6, and NFATC1 genes with the risk and development of ONFH in 200 ONFH patients and 177 health controls of Chinese population with using Mass ARRAY® platform. The results showed that the recessive model of NFATC1rs9518 was significantly associated with increased ONFH risk (OR:8.223, P=0.048); the proportion of stage Ⅳ patients in the rs9518TC genotype carriers was statistically higher than that of stage Ⅲ patients (P=0.03); in the T-C haplotype carriers of Naftac1, the proportion of bilateral hips lesions was also significantly enhanced than that of unilateral hip lesions(P=0.05). In addition, the proportion of idiopathic ONFH in the TT genotype carriers of OPGrs2073617 was significantly higher than that of steroid or alcohol-induced ONFH, respectively, while in the TC genotype carriers of the SNP, the proportion of idiopathic ONFH remarkably decreased compared with that of Alcohol-induced ONFH, P=0.021. Our results were first found that NFATC1rs9518 closely associated with the risk and the development of ONFH, while OPGrs2073617 statistically correlated with the etiological classification of ONFH.

Keywords: NFATC1.; ONFH; RANKL/RANK/OPG pathway; TRAF6; gene polymorphism.

MeSH terms

Aged
China
Female
Femur Head Necrosis / genetics*
Femur Head Necrosis / physiopathology
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Haplotypes / genetics
Humans
Male
Middle Aged
NFATC Transcription Factors / genetics*
Osteonecrosis / genetics*
Osteonecrosis / physiopathology
Osteoprotegerin / genetics*
Polymorphism, Single Nucleotide / genetics
RANK Ligand / genetics
Receptor Activator of Nuclear Factor-kappa B / genetics
Signal Transduction / genetics
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / genetics

Substances

NFATC Transcription Factors
NFATC1 protein, human
Osteoprotegerin
RANK Ligand
Receptor Activator of Nuclear Factor-kappa B
TNFRSF11A protein, human
TNFRSF11B protein, human
TNFSF11 protein, human
TRAF7 protein, human
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins