Institute of Endemic Diseases, School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Commission of the People's Republic of China, Xi'an, Shaanxi 710061, PR China.
Institute of Endemic Diseases, School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Commission of the People's Republic of China, Xi'an, Shaanxi 710061, PR China.
Bone. 2019 Mar;120:239-245. doi: 10.1016/j.bone.2018.03.026. Epub 2018 Apr 10.
The aim of the study was to investigate the association between rs5859 in Sep15, rs1139793 in TrxR2 polymorphisms with the risks of KBD and to detect the expression of AP-1 pathway in KBD subjects and in vitro. 208 KBD and 206 control subjects were included. PCR-Restriction Fragment Length Polymorphism (RFLP), Amplification Refractory Mutation Specific-PCR (ARMS-PCR) and Western Blotting were conducted. The results showed the minor A-allele frequency of rs5859 in KBD was statistically significantly higher than that in the control group (P < 0.05). The cases carrying A-allele had a 2-fold (95%CI: 1.064-3.956) increased risk of developing KBD compared with the G-allele carriers. There was no significant difference in genotype and allele distribution of rs1139793 between KBD patients and controls (P > 0.05). The frequency of the minor A allele of rs5859 was significantly different in Chinese healthy population compared with European, African and American. The frequency of the minor A allele of rs1139793 showed significant difference when compared with African and American. The levels of JunB, JunD, P65 proteins in KBD group were higher than those in control group (P < 0.0001). The expression of JunB, JunD, P65 proteins all increased in tBHP-induced C28/I2 oxidative damage model compared with control group (P < 0.05) and decreased after Se supplementation. Our finding indicated Sep15 is a possible candidate susceptibility gene for KBD. Combined with the in vitro study, our studies reveal novel insights into the mechanism of Se supplementation as an antioxidant via inhibiting the AP-1 signaling pathway in patients with KBD.
本研究旨在探讨 Sep15 中的 rs5859 和 TrxR2 多态性中的 rs1139793 与 KBD 风险之间的关联，并在体外检测 KBD 患者和体外中 AP-1 通路的表达。纳入了 208 例 KBD 患者和 206 例对照组。进行了 PCR-限制性片段长度多态性（RFLP）、扩增抗性突变特异性-PCR（ARMS-PCR）和 Western Blotting。结果显示，KBD 组 rs5859 的 minor A-allele 频率明显高于对照组（P < 0.05）。与 G-allele 携带者相比，携带 A-allele 的病例发生 KBD 的风险增加了 2 倍（95%CI：1.064-3.956）。rs1139793 的基因型和等位基因分布在 KBD 患者和对照组之间无显著差异（P > 0.05）。与欧洲、非洲和美洲的健康人群相比，rs5859 的 minor A 等位基因频率在中国健康人群中差异显著。与非洲和美洲人群相比，rs1139793 的 minor A 等位基因频率差异显著。KBD 组 JunB、JunD、P65 蛋白水平高于对照组（P < 0.0001）。tBHP 诱导的 C28/I2 氧化损伤模型中 JunB、JunD、P65 蛋白的表达均高于对照组（P < 0.05），补硒后表达降低。我们的发现表明，Sep15 可能是 KBD 的一个候选易感基因。结合体外研究，我们的研究揭示了硒补充作为抗氧化剂通过抑制 KBD 患者的 AP-1 信号通路发挥作用的新机制。
