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

Abstract

Background: Gene polymorphism 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, steroidinduced osteonecrosis of the femoral head (steroid-induced ONFH) is closely related to lipid metabolism level, so this study is intended to explore the relationship of RETN polymorphisms with susceptibility to steroid-induced ONFH in the Chinese Han population. Methods: In this case-control study, eight single-nucleotide polymorphisms (SNPs) of RETN were genotyped by the Agena MassARRAY system in 199 steroid-induced ONFH patients and 200 healthy controls. The relationship between RETN polymorphisms and steroid-induced ONFH risk was assessed using genetic models and haplotype analyses. Odds ratio (OR) and 95% confidence intervals (CIs) were obtained 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 two SNPs (rs34861192 and 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.

Steroid-induced osteonecrosis

“…Other SNPs with an impact on steroid-induced osteonecrosis have been demonstrated for cytochrome P450 and associated with lower risk [ 25 ], whereas different IL1B polymorphisms influence the risk for steroid-induced osteonecrosis [ 26 ]. Metalloproteinase 2, 8, and 10 polymorphisms contribute to susceptibility [ 27 , 28 ], as RETN (coding for resistin, an adipokine involved in metabolic disorders) and ApoA 5 and APOE (involved in lipid metabolism) SNP [ [29] , [30] , [31] ]. In contrast, metalloproteinase 9 SNPs appears to reduce the risk [ 32 ], similar to the gene for the tissue inhibitor of metalloprotease-4 [ 33 ], while the plasminogen activator inhibitor-1 (PAI-1) SNP has been demonstrated to be associated with an increased risk of steroid-induced osteonecrosis [ 34 ].…”

“… Gene Risk Ref. ATP-binding cassette subfamily B member 1 (ABCB1) Reduced [ 24 ] Cytochrome P450 Reduced [ 25 ] IL1B Increased or reduced [ 26 ] Metalloproteinase 2, 8, and 10 Increased [ 27 , 28 ] Metalloproteinase 9 Reduced [ 32 ] RETN Increased [ 29 ] APOA5 Increased [ 30 ] APOE Increased [ 31 ] TIMP4 Reduced [ 33 ] PAI-1 Increased [ 34 ] LncRNA LINC-PINT Increased [ 35 ] VEGF Increased [ 13 ] NO Increased [ 13 ] …”

RETN gene polymorphisms interact with alcohol dependence in association with depression

“…Moreover, rs1477341 was significantly correlated with an increased TG level and a decreased TC/HDL-C level. 19 In addition, it has been reported in the literature that the presence of the RETN rs3745368 A allele was associated with an increase in resistin level. 20 Hence, we conducted this study to assess whether RETN gene polymorphisms are related to depression susceptibility among individuals undergoing acute alcohol withdrawal (environment).…”

“…Moreover, rs1477341 was significantly correlated with an increased TG level and a decreased TC/HDL‐C level. 19 In addition, it has been reported in the literature that the presence of the RETN rs3745368 A allele was associated with an increase in resistin level. 20…”