• Jieli Du, Tianbo Jin, Yuju Cao, Junyu Chen, Yongchang Guo, Mingqi Sun, Jian Li, Xiyang Zhang, Guoqiang Wang, and Jianzhong Wang.
• Inner Mongolia Medical University, Hohhot, Inner Mongolia The College of Life Sciences, Northwest University National Engineering Research Center for Miniaturized Detection Systems, Xi'an, Shanxi Zhengzhou TCM Traumatology Hospital, Zhengzhou, Henan Department of Orthopedics and Traumatology, The 2th Affiliated Hospital of Inner Mongolia University, Hohhot, Inner Mongolia, China.
• Medicine (Baltimore). 2016 Sep 1; 95 (37): e4794e4794.

BackgroundSteroid-induced osteonecrosis of the femoral head (ONFH) is the most common clinical nontraumatic ONFH. Once ONFH occurs, it seriously reduces patients' quality of life. The matrix metalloproteinase/tissue inhibitor of metalloproteinase (MMP/TIMP) system was found to play a significant role in the development of ONFH. The aim of this study was to identify the associations between 7 genes selected from the MMP/TIMP system and steroid-induced ONFH.MethodsWe genotyped 34 single-nucleotide polymorphisms (SNPs) of 7 genes selected from the MMP/TIMP system in a case-control study with 285 cases of steroid-induced ONFH and 308 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.ResultsWe found that the minor alleles of rs1940475 and rs11225395 in MMP8 were associated with a 1.32-fold increased risk of steroid-induced ONFH in the allelic model analysis (P = 0.021 and 0.022, respectively). In the genetic model analysis, we found that rs3740938, rs2012390, rs1940475, and rs11225395 were associated with an increased risk of steroid-induced ONFH. In further stratification analysis, rs3740938 and rs2012390 displayed a significantly increased risk of steroid-induced ONFH in females under the dominant (rs3740938, OR = 2.69, 95% CI: 1.50-4.83, P = 0.001; rs2012390, OR = 2.30, 95% CI: 1.31-4.03, P = 0.012) and additive (rs3740938, OR = 2.02, 95% CI: 1.24-3.29, P = 0.010; rs2012390, OR = 1.77, 95% CI: 1.12-2.80, P = 0.047) models. In addition, haplotype "AGTCA" of MMP8 was found to be associated with a 1.40-fold increased risk of steroid-induced ONFH (95% CI: 1.04-1.88, P = 0.025).ConclusionOur results verify that genetic variants of MMP8 contribute to steroid-induced ONFH susceptibility in the population of northern China. In addition, we found that gender differences might interact with MMP8 polymorphisms to contribute to the overall susceptibility to steroid-induced ONFH.

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