大骨节病中SEPS1)-105G>A多态性和PI3K/Akt信号通路的作用

Role of selenoprotein S (SEPS1) -105G>A polymorphisms and PI3K/Akt signaling pathway in Kashin-Beck disease
2015-04-20 09:35发表评论
作者:Du, X.A., Wang, H.M., Dai, X.X., Kou, Y., Wu, R.P., Chen, Q., Cao, J.L., Mo, X.Y., Xiong, Y.M.
机构: 西安交通大学环境与疾病相关基因教育部重点实验室地方病研究所
期刊: OSTEOARTHR CARTILAGE2015年2月2期23卷

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% vs3.0%) and minor allele A (34.1% vs16.0%) 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 Gβγ, PI3Kp110, pAkt and pGSK3β in KBD group were higher than that in control group (all P<0.05). Gβγ, pAkt and pGSK3β 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. © 2014 Osteoarthritis Research Society International.

通讯机构: Institute of Endemic Diseases, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi'an, Shaanxi, China
学科代码:骨科学 整形外科学   关键词:大骨节病;SEPS1)-105G>A多态性;PI3K/Akt ,中国作者重要发表 爱思唯尔医学网, Elseviermed
来源: Scopus
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