A single-nucleotide polymorphism inMMP9is associated with decreased risk of steroid-induced osteonecrosis of the femoral head

Jieli Du,Huiqin Xue,Mingqi Sun,Wanlin Liu,Jianzhong Wang,Junyu Chen,Tianbo Jin,Xiyang Zhang,Guoqiang Wang,Zhenqun Zhao,Rui Bai

doi:10.18632/oncotarget.12034

Abstract

Osteonecrosis of the femoral head (ONFH) is a common hip joint disease, and steroid-induced ONFH accounts for a large number of cases. Here, we examined eight previously-identified single-nucleotide polymorphisms (SNPs) in the MPP2 and MPP9 genes of 285 steroid-induced ONFH patients and 507 healthy controls from northern China to determine whether these SNPs were associated with the risk of developing steroid-induced ONFH. Chi-squared tests and genetic model and haplotype analyses were used to evaluate associations. The rs2274755 SNP in MMP9 was associated with a decreased risk of steroid-induced ONFH in the allele, dominant, and additive models. Additionally, the “CGC” MMP9 haplotype was associated with a 0.69-fold decrease in the risk of steroid-induced ONFH. Although additional, larger population-based studies are needed to confirm these findings, our results reveal for the first time an association between a MMP9 SNP at the rs2274755 locus and a decreased risk of steroid-induced ONFH in a northern Chinese population.

Highlights

Osteonecrosis of the femoral head (ONFH) is a common hip joint disease that frequently causes disability
The “CGC” MMP9 haplotype was associated with a 0.69-fold decrease in the risk of steroid-induced ONFH
We examined whether harboring the minor allele for each single-nucleotide polymorphisms (SNPs) compared to the wild-type allele represented a risk factor in the genetic models shown in Table 3. rs2274755 polymorphism in the MMP9 gene conferred a protective effect against steroid-induced ONFH in the dominant model both before (OR = 0.66, 95% confidence intervals (CIs): 0.47–0.94, p = 0.019) and after adjustment for age and gender (OR = 0.68, 95% CI: 0.47–0.98, p = 0.034), and in the additive model both before (OR = 0.70, 95% CI: 0.51–0.96, p = 0.022) and after adjustment for age and gender (OR = 0.70, 95% CI: 0.51–0.98, p = 0.033)

Summary

Introduction

Osteonecrosis of the femoral head (ONFH) is a common hip joint disease that frequently causes disability. MMP-2 expression is upregulated in osteoarthritic cartilage [9], and MMP-9, which regulates growth plate angiogenesis and apoptosis of hypertrophic chondrocytes, may be essential for normal bone remodeling [10]. Both MMP-2 and MMP- 9 expression are increased in the joints of rheumatoid arthritis patients [11, 12]. MMP-2 mRNA and protein levels are up-regulated in ONFH subjects, while MMP-9 protein is overproduced in osteoarthritic bone www.impactjournals.com/oncotarget tissue [8]. MMP-9 expression may serve as a marker of efficacy in the treatment of steroid-induced osteonecrosis using ACTH. MMP-2 and MMP-9 expression, which were both higher in steroid-induced ONFH patients than in controls, have only recently been investigated in Chinese populations

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Conclusion