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.