Variants in RETN gene are associated with Steroid-induced osteonecrosis of the femoral head risk among Han Chinese People [post]

2019 unpublished
Introduction Gene polymorhisms has an important influence on RETN gene expression level, and the increased level of resistin encoded in RETN will lead to metabolic disorder, especially lipid metabolism. Moreover, steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) is closely related to lipid metabolism level, so this study aims to explore the association of RETN Polymorphisms with susceptibility to steroid-induced ONFH in the Chinese Han Population. Methods In this
more » ... ds In this case-control study, eight single nucleotide polymorphisms (SNPs) of RETN were genotyped by Agena MassARRAY system in 199 steroid-induced ONFH patients and 200 healthy controls. The association between RETN polymorphisms and steroid-induced ONFH risk was evaluated using genetic models and haplotype analyses. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated by logistic regression adjusted for age. Results We found significant differences in the distribution of HDL-C, TG/HDL-C, and LDL-C/HDL-C between the patients and the control group (p < 0.05). In allele model and genotype model analysis, rs34861192, rs3219175, rs3745368 and rs1477341 could reduce the risk of steroid-induced ONFH. Further stratified analysis showed that rs3745367 was related to the clinical stage of patients, and rs1477341 was significantly correlated with an increased TG level and a decreased TC/ HDL-C level. The Linkage analysis showed that three SNPs (rs34861192, rs3219175) in RETN even significant linkage disequilibrium. Conclusions Our results provide the firstly evidence that RETN gene polymorphisms were associated with a reduced risk of steroid-induced ONFH in Chinese Han Population. damage the hip joint and seriously reduces the patients quality of life and is difficult to reverse [3]. However, it is challenging to fully elucidate the pathogenesis of steroid-induced ONFH due to the various effects of steroids on multiple systems involved in osteoblast differentiation, osteoblast and osteoclast apoptosis, lipid metabolism, calcium metabolism and coagulation [4]. Some studies have shown that only a subset of patients develop ONFH within a few weeks of hormone therapy, suggesting that genetic factors may determine susceptibility to steroid-induced ONFH) [5]. Single-nucleotide polymorphisms (SNPs) are the most frequent variation that occurs in a single nucleotide at a specific position in the genome. Numerous SNPs have been identified through sequencing, and many of them in critical genes such as MMP-8 [1], MMP-9 [6], MMP-14 [7],ABCB1 [8], and VEGFA [9] were demonstrated to be associated with steroid-induced ONFH susceptibility. RETN, also known as ADSF and FIZZ3, is located on chromosome 19p13. RETN gene encodes resistin, which is a hormone secreted by fat cells and belongs to the cystein-rich C-terminal domain proteins called resistin-like molecules [10]. It was first observed in adipocytes, then in monocytes, macrophages, and the spleen, and more importantly, in human sebaceous glands and cultured sebaceous glands [11]. Some studies have demonstrated that elevated levels of resistin lead to metabolic disorders, which in turn are associated with diabetes, non-insulin dependent, acquired systemic lipodystrophy, as well as rheumatoid arthritis and the like [12-14]. Most importantly, it is the product of the secretion of fat cells and its related pathways include lipogenesis [15]. Elevated levels of resistin may also contribute to lipid metabolism disorders [14]. However, lipid metabolic disorders can lead to steroid-induced ONFH, so we believe that RETN can also induce steroid-induced osteonecrosis by affecting lipid metabolism. Considering the importance of resistin expression in lipid metabolism and the influence of its promoter and intron regional polymorphism on RETN expression, we hypothesized that the polymorphisms site of RETN might influence steroid-induced osteonecrosis. Moreover, to our knowledge, there are no previous studies have investigated the association of risk of steroid-induced ONFH and RETN polymorphisms. Therefore, we conduct a case-control study to evaluate the possible relationship of RETN gene polymorphisms at allele, genotype, and haplotype interface with 1.Association between genetic polymorphisms of MMP8 and the risk of steroid-induced osteonecrosis of the femoral head in the population of northern China. Medicine 2016, 95(37):e4794. 2.Wang A, Ren M, Wang J: The pathogenesis of steroid-induced osteonecrosis of the femoral head: A systematic review of the literature. Izawa H et al: Epigenome-wide association study suggests that SNPs in the promoter region of RETN influence plasma resistin level via effects on DNA methylation at neighbouring sites. 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doi:10.21203/rs.2.15695/v1 fatcat:czscm3svefcnlbsqnooxtdhzd4