Role of selenoprotein S (SEPS1)-105G>A polymorphisms and PI3K/Akt signaling pathway in Kashin-Beck disease

Objective: To investigate the relationship between SEPS1 polymorphism and phosphatidylinositol 3-kinase PI3K)/Akt signaling pathway in Kashin-Beck disease (KBD) and further explore the pathogenesis of KBD. Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect SEPS1 -105G> A polymorphism in 232 cases and 331 controls. The protein expressions of PI3K/ Akt signaling molecules in whole blood and chondrocytes were detected by Western blot. Results: The frequencies of SEPS1 -105G>A genotype AA (21.1% vs 3.0%) and minor allele A(34.1% vs 16.0%) in KBD are significantly higher than those in controls (OR: 8.020, 95% confidence interval (95% CI) 6.341-10.290, P < 0.0001; OR: 2.470, 95% CI 2.001-4.463, P < 0.0001, respectively). SEPS1 AA genotype was an independent risk factor for KBD (adjusted OR: 9.345, 95% CI 4.254-20.529; P < 0.0001). The expression of G beta gamma, PI3Kp110, pAkt and pGSK3 beta in KBD group were higher than that in control group (all P < 0.05). G beta gamma, pAkt and pGSK3 beta protein expression of AA and GA increased than GG (all P < 0.05). Cell apoptosis was increasing and molecule expression of PI3K/ Akt signaling pathway were up-regulated in the tert-Butyl hydroperoxide (tBHP)-injured group, the cell apoptosis and expression levels of PI3K/ Akt in Na2SeO3 group were decreased. Conclusions: The SEPS1 -105G> A is associated with an increased risk of KBD and influences the expression of PI3K/ Akt signaling pathway in KBD patients. Apoptosis induced by tBHP in chondrocyte might be mediated via up-regulation of PI3K/ Akt, Na2SeO3 has an effect of anti-apoptosis by down-regulating of PI3K/ Akt signaling pathway. (C) 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.