title: Role of selenoprotein S (SEPS1) -105G>A polymorphisms and PI3K/Akt signaling pathway in Kashin-Beck disease.
abstract: 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 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.
authors.affiliation: 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 710061, PR China.
authors.forename: X A
authors.initials: XA
authors.lastname: Du
authors.affiliation: 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 710061, PR China.
authors.forename: H M
authors.initials: HM
authors.lastname: Wang
authors.affiliation: 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 710061, PR China.
authors.forename: X X
authors.initials: XX
authors.lastname: Dai
authors.affiliation: School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Kou
authors.affiliation: 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 710061, PR China.
authors.forename: R P
authors.initials: RP
authors.lastname: Wu
authors.affiliation: 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 710061, PR China.
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.affiliation: 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 710061, PR China.
authors.forename: J L
authors.initials: JL
authors.lastname: Cao
authors.affiliation: School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, PR China.
authors.forename: X Y
authors.initials: XY
authors.lastname: Mo
authors.affiliation: 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 710061, PR China. Electronic address: xiongym@mail.xjtu.edu.cn.
authors.forename: Y M
authors.initials: YM
authors.lastname: Xiong
mesh_terms: D016022:Case-Control Studies; D005260:Female; D006801:Humans; D057767:Kashin-Beck Disease / Q000209:etiology* / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D058539:Phosphatidylinositol 3-Kinase / Q000502:physiology*; D011110:Polymorphism, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051140:Selenoproteins / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D008565:Membrane Proteins; C487710:SELENOS protein, human; D051140:Selenoproteins; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: Kashin-Beck disease; PI3K/Akt signaling pathway; Polymorphism; SEPS1