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

// Yuxin Qi 1, 2, * , Yong Zhu 2, * , Yuju Cao 3 , Huiqiang Wu 4 , Mingqi Sun 2 , Hao Wu 2 , Linlin Pan 2 , Guoqiang Wang 2 and Jianzhong Wang 2 1 Inner Mongolia Medical University, Hohhot, Inner Mongolia 010050, China 2 Department of Orthopedics and Traumatology, The 2nd Affiliated Hospital of Inner Mongolia University, Hohhot, Inner Mongolia 010030, China 3 Zhengzhou TCM Traumatology Hospital, Zhengzhou, Henan 450016, China 4 Inner Mongolia Autonomous Region Hospital of Traditional Chinese Medicine, Hohhot, Inner Mongolia 010000, China * These authors have contributed equally to this work and should be considered co-first authors Correspondence to: Guoqiang Wang, email: wangguoqianggq@163.com Jianzhong Wang, email: wangjianzhong0503@126.com Keywords: case-control study; MMP3; single-nucleotide polymorphism; osteonecrosis of the femoral head Received: May 02, 2017      Accepted: July 26, 2017      Published: November 06, 2017 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.