MMP9 polymorphism is associated with susceptibility to non-traumatic osteonecrosis of femoral head in a Chinese Han population.

Yuan Liu,Yan Zhao,Xue Feng,Jianping Shi,Yuxin Qi,Yanfei Jia,Jianzhong Wang,Jieli Du,Yuju Cao,Tianbo Jin,Feimeng An

doi:10.18632/oncotarget.20463

Abstract

Non-traumatic osteonecrosis of femoral head (ONFH) is an orthopedic refractory disease with escalating morbidity in Chinese Han population. In our case-control study, we examined eight previously identified MMP9 single-nucleotide polymorphisms (SNPs) in 585 non-traumatic ONFH patients and 507 healthy individuals from northern China to determine whether these SNPs associated with the risk of developing non-traumatic ONFH. Genetic model and haplotype analyses were used to evaluate the association between SNPs and non-traumatic ONFH. MMP9 rs2274755 (OR, 0.740; 95% CI, 0.578-0.949; p = 0.017) was associated with a reduced risk of non-traumatic ONFH. After adjusting for age and gender, the logistic regression results showed that rs2274755 associated with a lower risk of non-traumatic ONFH in the dominant (OR=0.71, 95% CI: 0.54-0.94, p=0.016), overdominant (OR=0.73, 95% CI: 0.55-0.96, p=0.026) and log-additive (OR=0.74740; 95% CI, 0.578-0.949; p=0.017) models. In addition, the “TGC” haplotype of rs2274755 was associated with a 0.79-fold decrease in risk while the “CTC” haplotype associated with a 0.65-fold decrease risk of the non-traumatic ONFH. These results provide evidence that the MMP9 SNP at the rs2274755 locus is associated with a decreased risk of non-traumatic ONFH in a Chinese Han population.

Highlights

Non-traumatic osteonecrosis of the femoral head (ONFH) is a painful and progressive disorder of the hip joint, mainly affecting middle aged individuals 30-50 years old
In our case-control study, we examined eight previously identified MMP9 single-nucleotide polymorphisms (SNPs) in 585 non-traumatic ONFH patients and 507 healthy individuals from northern China to determine whether these SNPs associated with the risk of developing non-traumatic ONFH
We designed a case-control study examining the potential association between MMP2 and MMP9 polymorphism and non-traumatic ONFH in 585 nonwww.impactjournals.com/oncotarget

Summary

Introduction

Non-traumatic osteonecrosis of the femoral head (ONFH) is a painful and progressive disorder of the hip joint, mainly affecting middle aged individuals 30-50 years old. Genetic polymorphisms are gene variations found in about 1% of the general population, where they influence protein translation and the expression of related genes to contribute to disease susceptibility [1]. It is believed that genetic polymorphisms may be crucially involved in non-traumatic ONFH [2,3,4]. Matrix metalloproteinases (MMPs) are a family of 23 Zn2+-dependent endopeptidases. Their primary activities involve hydrolysis of the protein components of connective tissues such as extracellular matrix (ECM) and basement membranes [5]. MMPs can be subdivided into matrilysins, stromelysins, gelatinases, and collagenases [6]. The actions of MMPs in pathology can be grouped www.impactjournals.com/oncotarget

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