MMP‐14 single‐nucleotide polymorphisms are related to steroid‐induced osteonecrosis of the femoral head in the population of northern China

Abstract

Background Osteonecrosis of the femoral head ( ONFH ) is a refractory disease which frequently occurs in young and middle‐aged people. Recent studies indicated that MMP ‐14 played an important role in the development of chondrocytes, metabolism of osteoblasts as well as fate decision of hypertrophic chondrocytes. The aim of this study was to investigate the association between polymorphisms of MMP ‐14 and steroid‐induced osteonecrosis of the femoral head in the Chinese population. Methods We selected 7 SNP s (rs3751488, rs1003349, rs1042703, rs2236302, rs1042704, rs2236303, and rs2236304) on gene MMP ‐14 . Odds ratios ( OR s) and 95% confidence intervals ( CI s) were estimated using the chi‐squared test, genetic model analysis, haplotype analysis, and stratification analysis. Results We discovered that the genotype “G/G” of rs2236302 was associated with ONFH risk in the MMP ‐14 in the codominant model ( OR = 8.62, 95% CI = 1.07–69.46, p = 0.038) and recessive model ( OR = 8.86, 95% CI = 1.10–71.31, p = 0.013). Conclusions We have confirmed that the susceptive SNP s (rs2236302) of MMP ‐14 from the MMP s/ TIMP s system exhibit a significant association with increased risk of steroid‐induced ONFH in the population of northern China.

Microarray analysis of long‐noncoding RNAs and mRNA expression profiles in human steroid‐induced avascular necrosis of the femoral head

“…(4) Cell inflammation and apoptosis: steroids could increase osteoblastic and osteocytic apoptosis, disrupting the mechanosensory function of the osteocyte network and leading to collapse of the femoral head . (5) Gene and gene polymorphisms: high CYP3A gene expression may increase the risk of SAVNFH, and many genes, such as the RANK, RANKL, and BMP6 genes, may play important roles in AVNFH; in addition, the IL1B gene polymorphism and MMP14 single‐nucleotide polymorphisms may be associated with an increased risk of SAVNFH in Chinese populations . However, the exact molecular pathogenesis of SAVNFH remains unknown.…”

“…11 (5) Gene and gene polymorphisms: high CYP3A gene expression may increase the risk of SAVNFH, 12 and many genes, such as the RANK, RANKL, and BMP6 genes, may play important roles in AVNFH [13][14][15][16][17] ; in addition, the IL1B gene polymorphism 18 and MMP14 single-nucleotide polymorphisms may be associated with an increased risk of SAVNFH in Chinese populations. 19 However, the exact molecular pathogenesis of SAVNFH remains unknown.…”

Germline VWF/MPRIP and somatoplasm FGA variants synergically confer susceptibility to non-traumatic osteonecrosis of the femoral head

“…Theoretically, SOX9 might physically interact with RUNX2 and thereby inhibit osteogenesis of RUNT-domain transcription factor [11][12] . In addition, MMP8 rs11225394, MMP3 rs650108 and RS522616, as well as MMP14 rs2236302 signi cantly correlated with non-traumatic ONFH [13][14][15] . Furthermore, Clotting factor V, MTHFR and PAI-1 variants correlated with high coagulation or low brinolysis, which might promote intravascular coagulation or weaken thrombolysis, causing ischemic necrosis of the femoral head [16][17][18] .…”

Association between Genetic Polymorphisms of <b><i>MIR3142HG</i></b> and the Risk of Steroid-Induced Osteonecrosis of the Femoral Head in the Population of Northern China

“…Steroid-induced ONFH may be a polygenic disease, such as lipid metabolism-related genes (ApoA and ApoB), drug metabolizing enzymes (CYP), drug transporters (ABCB1and ABCG2), and drug target molecules (NR3C1). [3][4][5] For example, MMP-8, MMP-9, MMP-14, and TIMP4 [6][7][8][9] have been confirmed to be associated with steroid-induced ONFH risk.…”