The study on polymorphisms of Sep15 and TrxR2 and the expression of AP-1 signaling pathway in Kashin-Beck disease.

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.