Association between MMP-3 polymorphisms among Chinese patients with osteonecrosis of the femoral head.

Yuxin Qi,Mingqi Sun,Linlin Pan,Yong Zhu,Huiqiang Wu,Hao Wu,Jianzhong Wang,Yuju Cao,Guoqiang Wang

doi:10.18632/oncotarget.22313

Abstract

Many potential causative factors are related to the initiation and progression of osteonecrosis of the femoral head (ONFH). The matrix metalloproteinase/tissue inhibitor of metalloproteinases (MMPs/TIMPs) system was found to play a significant role in the development of ONFH. The aim of this study is to investigate the association between polymorphisms of MMP-3 and ONFH in the Chinese population. We selected 8 single-nucleotide polymorphisms (SNPs) in 2 genes selected from the MMPs/TIMPs system in a case–control study with 585 cases of ONFH and 507 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using the chi-squared test, genetic model analysis, haplotype analysis, and stratification analysis. We found that the minor allele of rs650108 and rs522616 (p<0.05) was assumed a risk allele compared to the wild-type allele. In the genetic model analysis, We observed two susceptibility SNPs additionally: rs650108, dominant model analyses (with adjustment: OR=0.73; 95%CI 0.56-0.95; p=0.017) and additive model analyses (with adjustment: OR=0.83; 95%CI 0.70-0.99; p=0.044); and rs522616 recessive model analyses (with adjustment: OR=1.52; 95%CI 1.07-2.14; p=0.018) and additive model analyses (with adjustment: OR=1.21; 95% CI 1.02-1.44; p=0.033). Our results verify that genetic variants of MMP3 contribute to ONFH susceptibility in the population of northern China. In addition, we found that gender differences might interact with MMP3 polymorphisms to contribute to the overall susceptibility to ONFH.

Highlights

Osteonecrosis of the femoral head (ONFH) is a debilitating bone disease in which patients experience the collapse of the joint cartilage and femoral head and a subsequent loss of joint function caused by abnormities in the fibrinolytic system and a disorder in the blood supply [1–3]
We discovered that rs650108 and rs522616 were associated with osteonecrosis of the femoral head (ONFH) risk in the MMP3
We confirmed for the first time that MMP3 genetic polymorphisms were associated with a risk of ONFH

Summary

Introduction

Osteonecrosis of the femoral head (ONFH) is a debilitating bone disease in which patients experience the collapse of the joint cartilage and femoral head and a subsequent loss of joint function caused by abnormities in the fibrinolytic system and a disorder in the blood supply [1–3]. Since this stubborn disease may seriously affect the quality of life for patients, a large number of researchers have kept an eye on the identification of risk factors for ONFH. MMPs and tissue inhibitor of matrix metalloproteases (TIMPs) expression and activity that may increase the ability to repair damaged bone matrix influencing the equilibrium between bone resorption and de novo bone formation in ONFH

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