title: Association between genetic polymorphisms of MMP8 and the risk of steroid-induced osteonecrosis of the femoral head in the population of northern China.
abstract: BACKGROUND
  Steroid-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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  We 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).
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: 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.
authors.forename: Jieli
authors.initials: J
authors.lastname: Du
authors.forename: Tianbo
authors.initials: T
authors.lastname: Jin
authors.forename: Yuju
authors.initials: Y
authors.lastname: Cao
authors.forename: Junyu
authors.initials: J
authors.lastname: Chen
authors.forename: Yongchang
authors.initials: Y
authors.lastname: Guo
authors.forename: Mingqi
authors.initials: M
authors.lastname: Sun
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Xiyang
authors.initials: X
authors.lastname: Zhang
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Wang
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Wang
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005271:Femur Head Necrosis / Q000139:chemically induced* / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005938:Glucocorticoids / Q000009:adverse effects*; D006239:Haplotypes; D006801:Humans; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics*
chemical_list: D005938:Glucocorticoids; D019714:Tissue Inhibitor of Metalloproteinases; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8