Background. Steroid-induced osteonecrosis of the femoral head is a relatively serious condition which seriously reduces patient quality of life. However, the pathogenesis of steroid-induced ONFH is still unclear. In recent years, more scholars have found that the pathogenesis of steroid-induced ONFH is related to susceptibility factors such as MMPs/TIMPs system. The main purpose of this study is to investigate the correlation between MMP2 and MMP10 gene polymorphisms and steroid-induced ONFH in Chinese Han population. Methods. Six SNPs in MMP2 and two SNPs in MMP10 were genotyped using Agena MassARRAY RS1000 system from 286 patients of steroid-induced ONFH and in 309 healthy controls. The association between MMP2 and MMP10 polymorphisms and steroid-induced ONFH risk were estimated by the Chi-squared test, genetic model analysis, haplotype analysis, and stratification analysis. The relative risk was estimated by odd ratios (ORs) and 95% confidence intervals (CIs). Result. We found that the minor TG allele of rs470154 in MMP10 was associated with an increased risk of steroid-induced ONFH (OR = 1.45, 95% CI, 1.03 – 2.05, p = 0.032). In the genetic model analysis, we found that rs2241146 in MMP2 gene and rs470154 in MMP10 gene showed a statistically significant association with increased risk of steroid-induced ONFH. The six SNPs (rs470154, rs243866, rs243864, rs865094, rs11646643, and rs2241146) showed a statistically significant association with different clinical phenotypes. Conclusion. Our results verify that genetic polymorphisms of MMP2 and MMP10 contribute to steroid-induced ONFH susceptibility in the population of Chinese Han population, and our study provides new insights into the role that MMP2 and MMP10 plays in the mechanism of ONFH.
Background Dysregulation of the OPG/RANK/RANKL signalling pathway is a key step in the occurrence of steroid-induced osteonecrosis of the femoral head (ONFH). This study aims to understand the degree of methylation of the OPG, RANK, and RANKL genes in steroid-related ONFH. Methods A case-control study was designed, including 50 patients (25 males and 25 females) and 50 matched controls. The European Molecular Biology Open Software Suite (EMBOSS) was used to predict the existence and location of CpG islands in the OPG, RANK, and RANKL genes. The Agena MassARRAY platform was used to detect the methylation status of the above genes in the blood of subjects. The relationship between the methylation level of CpG sites in each gene and steroid-related ONFH was analysed by the chi-square test, logistic regression analysis, and other statistical methods. Results In the CpG islands of the OPG, RANK, and RANKL genes in patients with steroid-related ONFH, several CpG sites with high methylation rates and high methylation levels were found. Some hypermethylated CpG sites increase the risk of steroid-related ONFH. In addition, a few hypermethylated CpG sites have predictive value for the early diagnosis of steroid-related ONFH. Conclusion Methylation of certain sites in the OPG/RANK/RANKL signalling pathway increases the risk of steroid-related ONFH. Some hypermethylated CpG sites may be used as early prediction and diagnostic targets for steroid-related ONFH.
Background Alcohol‐induced osteonecrosis of femoral head (ONFH) is a complex disease and genetic factors are one of the causes. The purpose of this study is to investigate the effects of RETN (resistin; OMIM: 605565) and LDLR (low density lipoprotein receptor; OMIM: 606945) polymorphisms on the risk of alcohol‐induced ONFH in Chinese Han population. Methods A case–control study including 201 patients and 201 controls was designed. Seven single nucleotide polymorphisms (SNPs) in RETN gene and four SNPs in LDLR gene were genotyped using Agena MassARRAY platform. In allele model and genetic model, chi‐square test and logistic regression were used to study the associations between these SNPs and ONFH susceptibility. In addition, the relationships between these SNPs, clinical phenotypes, and blood lipid level with one‐way analysis of variance were analyzed. Results In the allele model, rs7408174 and rs3745369 in RETN were associated with increased risk of alcohol‐induced ONFH, whereas rs34861192 and rs3219175 in RETN showed reduced risk of alcohol‐induced ONFH. In the genetic model, rs7408174 was associated with increased risk of alcohol‐induced ONFH in dominant model and log‐additive model. Rs3745369 showed an increased risk in codominant model, recessive model, and log‐additive model. Rs34861192 showed a decreased risk in codominant model, dominant model, and log‐additive model, and rs3219175 showed a decreased risk in dominant model and log‐additive model. The rs3745368 in RETN was associated with the clinical stage of the disease. Conclusion These results suggest that RETN genetic polymorphisms are associated with the susceptibility of alcohol‐induced ONFH in Chinese Han population.
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.
Background: The pathogenesis of non-traumatic osteonecrosis of the femoral head (ONFH ) is related to the interruption of blood supply caused by lipid metabolism and hypercoagulability. The purpose of this study was to explore the relationship between clinical biochemical parameters and non-traumatic ONFH. Methods: The basic information and biochemical indexes of 1292 patients with non- traumatic ONFH and 1880 healthy controls were collected. SPSS software (version 22.0) was used to process and analyze the data. T-test was used for quantitative analysis. Chi-square test was used for categorical variables.p< 0.05 were the index with statistical significance. Results: In the population sample, TC (p= 0.00004), LDL (p= 0.014) and PLT (p= 0.000005) levels were statistically significant between the two groups.In men, levels of TC (p = 0.004), LDL (p= 0.011), and PLT (p= 0.00005) were statistically significant between the two groups.In women, TC (p= 0.001) and PLT (p= 0.048) levels were statistically significant between the two groups.There were differences in TC (p= 0.00001) and PLT (p= 0.031) levels between the case group and the control group in samples aged less than 45 years.There were differences in LDL (p= 0.00002) and PLT (p= 0.022) levels between the two groups in samples older than 45 years.Compared with the control group, patients with alcohol-induced ONFH had HDL (p = 0.002).LDL (p= 0.00002);The level of PLT (p= 0.0001) was significantly different.HDL (p = 0.005) was found in alcohol-induced ONFH patients younger than 45 years of age.The PLT level (p=0.045) was different from that of the control group.There was a difference in LDL (p= 0.000003) levels between control and alcohol-induced ONFH patients older than 45 years.The older the onset age, the TC in vivo;HDL;LDL;ApoA1;ApoB;The lower the PLT level.With the prolongation of the onset time, the PLT level in the patient's body is decreasing continuously.Conclusion: The changes of biochemical indexes are closely related to the occurrence of non-traumatic ONFH. Our research can provide a new direction for the prevention of ONFH.
Background: The dysregulation of OPG/RANK/RANKL signaling pathway is a key step in the occurrence of steroid-induced osteonecrosis of the femoral head (ONFH). This study aims to understand the degree of methylation of OPG, RANK and RANKL genes in steroid-related ONFH.Methods: A case-control study was designed, including 50 patients and 50 controls. The Agena MassARRAY platform is used to detect the methylation status of OPG, RANK and RANKL genes in the blood of subjects. The relationship between the methylation level of the CpG site of each gene and the steroid-related ONFH was analyzed.Results: In the CpG islands of the OPG, RANK and RANKL genes of steroid-related ONFH patients, a number of CpG sites with high methylation rate and high methylation level were found. Some hypermethylated CpG sites increase the risk of steroid-related ONFH. In addition, by constructing the receiver operating characteristic (ROC) curve, we also discovered a few hypermethylated CpG sites, which have predictive diagnostic value for steroid-related ONFH.Conclusion: Methylation in the OPG / RANK / RANKL signaling pathway increases the risk of steroid-related ONFH. Some hypermethylated CpG sites can be used as early prediction and diagnostic targets for steroid-related ONFH.
<b><i>Background:</i></b> Steroid-induced osteonecrosis of the femoral head (ONFH) is aseptic necrosis of the femoral head caused by glucocorticoid use. Once necrotic femoral head necrosis occurs, it irreversibly affects the quality of life seriously. Studies have shown that the susceptibility to steroid-induced ONFH is likely to be related to the variation of miRNA-coding genes. Therefore, this study aimed was to investigate the effect of <i>MIR3142HG</i> on steroid-induced ONFH. <b><i>Methods:</i></b> Agena MassARRAY was used to genotype <i>MIR3142HG</i> gene rs1582417, rs2431689, rs7727155, and rs17057846 in 199 patients and 725 healthy people. A genetic model and haplotype analysis were used to evaluate the relationship between the <i>MIR3142HG</i> polymorphism and the risk of steroid-induced ONFH. The odds ratio and 95% confidence intervals were obtained through logistic regression to assess the influence of gene polymorphisms on the occurrence of steroid-induced ONFH. <b><i>Results:</i></b> The consequences show that rs7727115 is a protective factor, it could reduce the risk of steroid-induced ONFH, and rs1582417 could increase the risk of steroid-induced ONFH. In the genetic model, rs1582417 was associated with increased risk of alcohol-induced ONFH in dominant model and log-additive model. rs7727115 showed a decreased risk in codominant model, dominant model, and log-additive model. In addition, rs2431689 is related to HDL-C (<i>p</i> = 0.012) and ApoA1 (<i>p</i> = 0.010) levels, and rs17057846 (<i>p</i> = 0.024) is related to ApoB levels. Thelinkage analysis indicated 3 single-nucleotide polymorphisms (rs2431689, rs7727115, and rs17057846) in <i>MIR3142HG</i> with significant chain imbalance. In addition, haplotype “GGG” of <i>MIR3142HG</i> was found out and is harmful for steroid-induced ONFH. <b><i>Conclusion:</i></b> Our results first confirm that the genetic polymorphism of <i>MIR3142HG</i> is associated with steroid-induced ONFH susceptibility in Chinese Han population.
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