The Study On Expression of Ap-1 Signaling Pathway and Polymorphisms Of Sep15 and Trxr-2 Genes In Kashin-Beck Disease

Abstract

Kashin-Beck disease (KBD) is an endemic osteoarthropathy, and apoptosis of chondrocyte is its main pathological feature, which mainly distributed from northeastern to southwestern of China. However, the pathogenesis of KBD still remains unknown. Recent studies have found that selenoproteins SNP may influence the KBD susceptibility, and AP-1 pathway plays an important role for regulating apoptosis-related genes. Therefore, we performed this experiment to investigate the polymorphisms of Sep15 rs5859 and TrxR-2 rs1139793 as well as proteins expression of AP-1 pathway in KBD patients and controls for understanding KBD pathogenesis. 208 KBD patients and 206 control subjects from Shaanxi in China were included in this study. PCR-Restriction Fragment Length Polymorphism and Amplification Refractory Mutation Specific-PCR were used to detect Sep15 rs5859 and TrxR-2 rs1139793, respectively. The protein expression levels of AP-1 signaling pathway in whole blood from 20 KBD patients and 20 healthy controls were detected by Western blotting. The minor A-allele frequency of Sep15 rs5859 in KBD patients was significantly higher than that of control group (P＜0.05). The cases carrying A-allele had a 2-fold increased risk of developing KBD compared with the G-allele carriers (OR 95%CI: 1.064-3.956). There was no significant difference in genotype and allele distribution of TrxR-2 rs1139793 between KBD patients and controls. The expression levels of JUB and JUD in KBD group were higher than that in control group(P<0.0001). The frequency of the minor A-allele of Sep15 rs5859 is a risk factor for KBD. AP-1 signaling pathway is up-regulated in KBD patients, which might contribute to chondrocyte apoptosis of KBD (This research was supported by National Natural Science Foundation in China No.81573104，81172610，81673117).