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).Conclusion: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.

IL‐4 gene polymorphisms and their relation to steroid‐induced osteonecrosis of the femoral head in Chinese population

“…The Association Research Circulation Osseous (ARCO) classification system was used for radiographic evaluation (Table ) (Gardeniers, Gosling‐Gardeniers, & Rijnen, ; Gardeniers,). Steroid‐induced ONFH was defined by a history of a mean daily dose ≥16.6 mg or a highest daily dose of 80 mg of prednisolone equivalent within 1 year prior to the development of symptoms or radiological diagnosis in asymptomatic cases (Du et al, ; Eichelbaum, Fromm, & Schwab, ; Zhao, Li, & Guo, ). Participants were excluded on the basis of having traumatic ONFH, dislocation of the hip joint, with histories of drinking more than 400 ml ethanol per week, significant familial hereditary disease, or other hip diseases.…”

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

“…Viable transplantation studies show that MMP‐9 may be involved in bone regeneration mediated by stem cells (Mosig et al., ). In our previous study, we have demonstrated that MMP‐8,MMP‐9 single‐nucleotide polymorphisms are related to steroid‐induced ONFH in Chinese population (Du, Jin, et al., ; Du, Lin, et al., ).…”

Variants in RETN gene are associated with steroid-induced osteonecrosis of the femoral head risk among Han Chinese people

“…With the wide application of glucocorticoid in the treatment of rheumatic diseases, autoimmune diseases, hematopoietic system diseases, and other diseases, steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) has become the most common non-traumatic osteonecrosis of the femoral head (ONFH) type in clinical practice [1,2]. Epidemiological studies in East Asia have shown that 47.4% of all cases diagnosed as non-traumatic ONFH arose as a direct result of steroids [3].…”