Association of MIR17HG and MIR155HG gene variants with steroid-induced osteonecrosis of the femoral head in the population of northern China

Abstract

Introduction Steroid-induced osteonecrosis of the femoral head (ONFH) is a disease of the bone. Metabolism and genetic factors are generally considered to play an important role. The purpose of this study was to investigate the relationship between single-nucleotide polymorphisms (SNPs) in MIR17HG and MIR155HG and the risk of steroid-induced ONFH in the population of northern China. Methods A total of 199 steroid-induced ONFH patients and 506 healthy controls were recruited for the study. Four SNPs of MIR17HG and seven SNPs of MIR155HG were genotyped by Sequenom MassARRAY. ORs and 95% CIs were used to evaluate the relationship between these SNPs and steroid-induced ONFH. Results In the codominant model, patients with the MIR17HG SNPs (rs7318578) AA genotype had an increased risk of steroid-induced ONFH (OR = 1.79, p = 0.039); in the recessive model, patients with the MIR17HG SNP (rs7318578) AA genotype had an increased risk of steroid-induced ONFH (OR = 1.78, p = 0.032). Stratified analysis showed that a MIR17HG SNP (rs7318578) and the MIR155HG SNPs (rs77218221, rs11911469, rs34904192 and rs4143370) were closely related to different unornamented phenotypes of steroid-induced ONFH. Analysis of the clinical indicators revealed significant differences in high-density lipoprotein (HDL-C) levels between the ONFH group and the control group (p = 0.005). In the MIR17HG SNP (rs75267932), patients with different genotypes had different levels of triglyceride (TG). The MIR155HG SNPs (rs77699734, rs1893650, and rs34904192) showed differences in triglyceride (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) levels in patients with different genotypes. Conclusion Our results confirm that MIR17HG and MIR155HG gene mutations are associated with steroid-induced ONFH susceptibility in the population of northern China, providing new evidence for the early detection and prevention of ONFH.

Bioinformatics and Gene Expression Omnibus Analysis of Key Candidate Genes and Pathways Associated with Femoral Head Necrosis

“…Activation of MAPK8 (JNK) in FHN indicates its potential role in the disease process. Moreover, elevated p38 activity may contribute to the production of inflammatory cytokines like IL-1β and TNF-α, promoting dysfunction in osteoblasts and osteoclasts and ultimately causing bone tissue damage (26). Targeting p38 signaling has been explored as a potential therapeutic strategy for managing FHN.…”

Downregulation of growth plate genes involved with the onset of femoral head separation in young broilers

“…Another downregulated gene in broilers with 21 days of age was LEPR, which is involved with lipid metabolism and inflammatory response ( Abete et al, 2009 ; Gogiraju et al, 2019 ). Mutations in this gene has already been associated to femoral head osteonecrosis in humans ( Liu T. et al, 2021 ) and with bone integrity traits in broilers ( Ibelli et al, 2014 ). Although there is no information on its role associated with FHS in chickens, in mice, LEPR was considered a negative modulator of bone mechanosensitivity, leading to a poor osteogenic response ( Kapur et al, 2010 ).…”

Steroid-induced osteonecrosis

“…Significant methylation level differences between patients and controls were found in ABCB1 gene, with patients having higher methylation levels [ 25 ]. Micro RNAs (MIR) were also found to be implicated in risk of diseases, and the transcripts of MIR17HG and MIR155HG gene variants, which regulate bone metabolism among other functions, are associated with steroid-induced osteonecrosis [ 36 ].…”